The selection, acquisition, and use of high‐quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs
A select offering of Pharma-Developed bioactive small molecules, both approved therapeutics/drug candidates and tool compounds, is tailored for potential use in Late Stage Functionalization. The compounds selected can be modified to include fluorine, which, despite appearing sparingly in naturally-occurring compounds, is found in fully 25% of FDA approved drugs.

Solutions to incorporate fluorine into your Lead compound are explored further in our Fluorination Application Guide.

Specifically, phenolic and alkyl carbinols can be converted directly to fluorine using PhenoFluor, a late-stage deoxyfluorination reagent.
Bioisosteric replacement and scaffold hopping are twin methods used in drug design to improve the synthetic accessibility, potency and drug like properties of a compound and to move into novel chemical space. Bioisosteric replacement involves swapping functional groups of a molecule with other functional groups that have similar biological properties. Scaffold hopping is the replacement of the core framework of a molecule with another scaffold that will improve the properties of the molecule or to find similar potent compounds that exist in novel chemical space. This review outlines the key concepts, importance and challenges of both methods using examples and comparisons of techniques available for finding bioisosteric replacements and scaffold hops. There are many methods available for bioisosteric replacement and scaffold hopping, all with their own advantages and disadvantages. Drug design projects would benefit from a combination of these methods to retrieve diverse and complimentary ...
Emerald BioStructures (formerly deCODE biostructures) announced a publication in the December 27, 2009 advance online issue of Nature Biotechnology, detailing the application of structure-based drug design (SBDD) to engineer ...
Many hematopoietic and nonhematopoietic diseases require chemotherapy and radiotherapy for treatment. Unfortunately, these regimens induce long-term damage, deleterious side effects and require multiple treatments for success. Hematopoietic stem cell (HSC) transplantation has proven effective in treatments but requires HLA-matching of these products to prevent complications, a process not easily achieved. Umbilical cord blood has become a standard in therapeutic transplantation primarily due to the ability to avoid more stringent HLA-matching. However, the low stem cell numbers in cord blood which limits use primarily in pediatric patients requires ex vivo expansion to increase patient availability. Clinical expansion is difficult to achieve and costly necessitating the need for enhanced protocols. The recent identification of inducing pluripotency by small molecule compounds has become an attractive option in HSC expansion. Our aim was to identify compounds that could induce self-renewal ...
Staphylococcus aureus quickly develops resistance to antibiotics and poses a significant health threat to humans. New antibiotic targets are needed for the development of new antibiotics. Trans-translation has important roles in maintaining bacterial viability. Small molecules, KKL-35 and KKL-40, were recently identified as specific inhibitors of trans-translation. We have investigated the roles of trans-translation on S. aureus viability and the potential of KKL-35 and KKL-40 as antibiotics. We find that KKLs show bactericidal activity against multiple S. aureus strains at relatively low concentration. We also find that sub-lethal doses of KKLs make S. aureus more susceptible to antimicrobials. Neither KKL-35 nor KKL-40 are cytotoxic to human HeLa cells. Unfortunately, KKL-40 is inactivated by human serum. Therefore, new inhibitors will need to be identified in future studies. Notably, the development of resistance by S.aureus against KKLs remains at a low level. Therefore trans-translation is ...
Scientists at the University of Duesseldorf and the University of Erlangen have developed new small molecules which can be used for the treatment of diseases characterized by the presence of misfolded proteins. Examples for such medical conditions are prion diseases, e.g. CJD, as well as neurodegenerative (e.g. Alzheimers disease) or neuropsychiatric diseases. Compo-Q have a structural relationship to quinacrine which is considered to be one of the most promising candidate for the clinical therapy of prion diseases. In Compo-Q the "modified quinacrine" is covalently linked to a derivative of another substance which has been proven effective against prion diseases in vitro ...
Scientists at the University of Bonn have identified new small molecules which can be used for the treatment of diseases characterized by alterations of proteins which are affected by Guanine nucleotide Exchange Factors (GEFs). Proteins targeted by GEFs are involved in integrin signalling, vesicle transport, or MAPK-signalling. These processes play an important role in the modulation of the immune response. Therefore, abnormal activation of the target proteins of GEFs can cause autoimmune and tumor diseases in humans ...
Walczak M, Ganesan SM, Niles JC, Yeh E. (2017) ATG8 is essential specifically for an autophagy-independent function in apicoplast biogenesis in blood-stage malaria parasites. mBio (In press). Gisselberg JE, Herrera Z, Altenhofen L, Llinas M, Yeh E. (2017) Specific inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase in malaria parasites via a new small molecule binding site. Cell Chemical Biology (In press) (Preprint) Amberg-Johnson K, Hari SB, Ganesan SM, Lorenzi HA, Sauer RT, Niles JC, Yeh E. (2017) "Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens." eLife. doi: 10.7554/eLife.29865 (PubMed) (PDF). Gisselberg JE, Zhang L, Elias JE, and Yeh E. "The prenylated proteome of Plasmodium reveals pathogen-specific prenylation." Mol Cell Proteomics. 2016 Dec. doi: 10.1074/mcp.M116.064550. (PubMed) (PDF). Wu W, Herrera Z, Ebert D, Baska K, DeRisi JL, Yeh E (2014) "A chemical rescue screen identifies a Plasmodium falciparum apicoplast ...
Hello, I am applying for a PhD position in Chemistry and my motivation letter need to be checked. Thank you Dear Mr., I am an undergraduate student and as my CV indicates in June of this year I expect to receive B. Sc. degree in Chemistry and in 2015 M. Sc. degree. In future, I see myself only as a researcher, so after graduation I want to continue my education as a PhD student. On my part your projects devoted to synthesis of new small molecule modulators and synthetic approach to
BioAssay record AID 686955 submitted by ICCB-Longwood/NSRB Screening Facility, Harvard Medical School: A confirmatory screen for small compounds that change glucocorticoid sensitivity in NFkB suppression.
A unique collection of 254 small molecule modulators with biological activity used for epigenetics research and associated assays. • The library contains epigenetics-related compounds targeting HDAC, Histone Demethylase, Histone Acetyltransferase (HAT), DNA Methyltransferase (DNMT), Epigenetic Reader Domain, MicroRNA, etc. • A valuable tool for chemical genomics, epigenetic target identification in pharmacogenomics, and other biological applications. • Bioactivity and safety confirmed by preclinical research and clinical trials. Some compounds have been approved by FDA.. • Structurally diverse, medicinally active, and cell permeable.. • Rich documentation with structure, IC50, and other chemical & biological data. • NMR and HPLC validated to ensure the highest purity. • All compounds are in stock and continuously updated. ...
The NIH Molecular Libraries Program (MLP) was founded to translate the discoveries of the Human Genome Project into therapeutics through a network of high-throughput screening (HTS) centers. A decade of discovery produced hundreds of probes - highly selective small molecules that modulate cellular function - but centralized compound screening bears the same cost and infrastructure burdens of millennial DNA sequencing centers, which has limited access to the technology and, more significantly, the rate of small molecule discovery. We are building a next-generation distributable drug discovery platform analogous to next-generation DNA sequencing. We have developed DNA-encoded solid-phase synthesis strategies to produce ultra-miniaturized compound libraries where each microscopic bead displays many copies of a small molecule library member and a corresponding amplifiable DNA that that encodes the structure. In parallel, we engineered microfluidic instrumentation for miniaturizing automated ...
3261 Genetic instability can lead to tumorigenesis, creating the need for cells to develop mechanisms and checkpoints to ensure faithful replication and division of genetic material. These mechanisms and checkpoints remain intact in normal cells, but are often disrupted or lost in cancer cells. Aurora kinases have mitotic regulatory functions and are important proteins in the maintenance of genetic stability, especially during mitosis. Aurora A localizes to the centrosomes during mitosis and is required for spindle assembly; atypical amounts of Aurora A in cells cause abnormal spindle formation and disruption of the spindle-assembly checkpoint. Overexpression of Aurora has been observed in several types of human cancers including breast, colorectal, prostate, ovarian, and pancreas. Aurora A represents a logical target because of its implication in tumorigenesis and, being a kinase, lends itself to small molecule inhibition. We have developed new small molecule inhibitors, the MP529 series, which ...
The research community has enhanced access to authentic, high-quality Pfizer compounds through Sigma Life Science. To further research in drug discovery, over 175 authentic, quality-controlled Pfizer probes and drugs compounds are available for multiple research areas, fostering reproducibility, innovation, and discovery. To learn more about Pfizers partnership with Sigma and to view Pfizer compounds for your area of research, visit sigma.com/bsm-pfizer ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
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In a differential cytotoxicity screen, we identified a novel small molecule modulator of phosphodiesterase 3A (PDE3A) that kills cancer cells expressing elevated levels of PDE3A and SLFN12 (de Waal, Nat Chem Biol, 2016). Treatment with this cell-selective cytotoxic small molecule, DNMDP, induces complex formation between PDE3A and SLFN12, resulting in apoptosis. Inhibition of PDE3A enzymatic activity is not sufficient for cancer cell killing, and expression of both PDE3A and SLFN12 are required. Although the mechanism of signaling to the apoptosis machinery remains unclear, we examined more closely the role of the PDE3A-SLFN12 complex in cancer cell killing mediated by DNMDP. We found that cancer cell lines made resistant to DNMDP by persistent exposure downregulated SLFN12 expression and that re-expression of SLFN12 was sufficient to restore sensitivity. Furthermore, ectopic expression of PDE3A and SLFN12 are sufficient to sensitize cancer cells to DNMDP. These data underscore the tight ...
DNA-encoded chemical libraries (DEL) is a technology for the synthesis and screening on unprecedented scale of collections of small molecule compounds. DEL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology. The aim of DEL technology is to accelerate the drug discovery process and in particular early phase discovery activities such as target validation and hit identification. DEL technology involves the conjugation of chemical compounds or building blocks to short DNA fragments that serve as identification bar codes and in some cases also direct and control the chemical synthesis. The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single-tube approach. In contrast ...
Small molecules offer exciting opportunities for plant science. So far, bioactive small molecules have been identified as plant hormones, herbicides, growth regulators, or taken from animal research. Recently, plant scientists have started to explore further the chemical space for novel modulators of plant hormone signalling, and have followed up this work with exciting discoveries illustrating the potential of small molecules such as brassinazole and sirtinol. New chemical genetic screens have been designed to generate chemical tools for the investigation of membrane trafficking, gravitropism and plant immunity. Further novel chemetic tools to identify targets and modes of action are currently generated through an intimate interdisciplinary collaboration between biologists and small molecule chemists.
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In addition, many E3s have been implicated in human disease and are attractive targets for drug discovery. However, currently no small molecule modulators for this class of enzymes have reached the clinic. Each E3 enzyme targets a small number of proteins for Ub modification but the exact substrates are mostly unknown and their identification continues to be a challenge. E3 ligase enzymes are a large (> 500) and complex super- family, many of which contain binding domains to interact with ubiquitin, E2 enzymes and substrate proteins. In addition to substrate ubiquitination, many E3 ligases can also self- or auto-ubiquitinate in the presence of an E2 enzyme, a property that may be used as an auto-regulatory mechanism to control its own intracellular levels. In general, the detailed molecular mechanism, stoichiometries and linkage site selection of E3 enzymes are poorly understood. As with ubiquitin E3 ligases, similar activities are also part of the final conjugation processes for other UBL ...
Vasoactive intestinal peptide (VIP) is a neuroendocrine peptide that has been implicated in a myriad of functions. VIP promotes neuronal survival during development and apoptotic challenges. Further, VIP has been shown to regulate hormonal release, circadian rhythms, vasodilation, and T cell proliferation in central and peripheral tissues. VIP binds with equally high affinity to VPAC1 and VPAC2 receptors, members of the Class B family of G protein-coupled receptors (GPCRs) that also include the PAC1, glucagon (GCGR), and CRH receptors. VIP binding has previously been shown to increase downstream MAPK signaling cascades, especially MEK/ERK. Given the structural similarities and functional overlap between VPAC1 and VPAC2 receptors, we sought to investigate whether there are small molecule modulators that can probe and identify the functional distinctions between the two receptor subtypes. For these studies, we used HEK-293 cells stably expressing the VPAC1-EGFP or the VPAC2-EGFP receptor. The cultures
Sandhya Kortagere, PhD, is an associate professor in the Department of Microbiology & Immunology at Drexel University College of Medicine. She is interested in designing and developing small molecule modulators to treat neurodegenerative diseases.
Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. We synthesize biologically interesting natural products and screen small molecule libraries to identify modulators of biological processes. Then, we explore their modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. In addition, we design and develop unique and efficient synthetic strategies that will allow rapid access to molecular complexity and structural diversity. Through multidisciplinary approaches, including organic synthesis, molecular biology, and cell biology, the cellular components and molecular events that embody cancer, immune response, and GPCR signaling have systematically been explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases. ...
Research in the Hong group focuses on using chemical tools, in particular small molecules, to understand the signaling pathways in biology. We synthesize biologically interesting natural products and screen small molecule libraries to identify modulators of biological processes. Then, we explore their modes of action in order to investigate intracellular signaling pathways and identify novel targets for drug design. In addition, we design and develop unique and efficient synthetic strategies that will allow rapid access to molecular complexity and structural diversity. Through multidisciplinary approaches, including organic synthesis, molecular biology, and cell biology, the cellular components and molecular events that embody cancer, immune response, and GPCR signaling have systematically been explored. Compounds employed in these studies could also advance the development of novel therapeutics for the treatment of human diseases. ...
Atomwise announced the launch of a ten billion compound AI-powered virtual drug screening initiative, the 10-to-the-10 program, in collaboration with Enamine, the worlds largest chemical supplier. The initiative aims to dramatically increase the discovery of safer small molecule drugs to treat pediatric cancers.. Atomwise will use its patented AI virtual screening technology to evaluate the binding of billions of drug-like molecules to cancer target proteins, and Enamine will provide support and access to a virtual library of ten billion small molecule compounds. The research will be directed by the needs of innovators in cancer research at leading universities.. Cancer is diagnosed in more than 15,000 children and adolescents each year. Many cancers do not have effective treatments and for those that do, it is estimated that 80% have serious adverse effects that impact long-term health. Therefore, new oncology drugs are needed. The 10-to-the-10 program will search for novel drug candidates by ...
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Video articles in JoVE about high content screening include Ordering Single Cells and Single Embryos in 3D Confinement: A New Device for High Content Screening, A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening, High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC), Generation and Multi-phenotypic High-content Screening of Coxiella burnetii Transposon Mutants, High Content Screening in Neurodegenerative Diseases, High Content Screeningはゆゆェソトリゲェトは祥絍紬胧は毐怣ェトソェ - ADVERTISEMENT, A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos, A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules, A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform, 3D Microtissues for Injectable Regenerative Therapy and
The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.. Research Areas: biophysics, enzymes, cell biology, uracil, cancer, HIV, DNA, RNA ...
Rebecca A. Wingert is the author of these articles in the Journal of Visualized Experiments: Dissection of the Adult Zebrafish Kidney, Laser Ablation of the Zebrafish Pronephros to Study Renal Epithelial Regeneration, Production of Haploid Zebrafish Embryos by In Vitro Fertilization, Flat Mount Preparation for Observation and Analysis of Zebrafish Embryo Specimens Stained by Whole Mount In situ Hybridization, Analysis of Nephron Composition and Function in the Adult Zebrafish Kidney, A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos
CRO Prestwick Chemical offers smart chemical screening libraries, medicinal chemistry services to accelerate development of innovative small molecule drugs
Chemical Genetics: We use C. elegans as a model system to model a variety of diseases, including neurodegeneration, mood disorders, muscle excitability, and helminthic infection. We use these models in high-throughput screens for novel drug leads, collaborate with other labs to test our hits in more complex systems, and then return to C. elegans to better understand the mechanism of action of the bioactive small molecules. ...
Free Online Library: Samaritan Discovers Long-Sought-After Small Molecule Drug That Induces Human Neuron Differentiation. by Business Wire; Business, international
TheInfoList.com - (DNA-encoded_chemical_library) Contents1 DNA-encoded chemical libraries and display technologies 2 History 3 Non-evolution based technologies3.1 Split-&-Pool DNA DNA Encoding 3.2 Stepwise coupling of coding DNA DNA fragments to nascent organic molecules 3.3 Combinatorial self-assembling3.3.1 Encoded self-assembling chemical libraries4 Evolution-based technologies4.1 DNA-routing 4.2 DNA-templated synthesis5 3-Dimensional proximity-based technology (YoctoReactor technology)5.1 Building a yR library 5.2
We have pulled the foundational disciplines of chemical biology into one seamless collaborative unit. CBT - under the direction of Jeff Porter - will innovate new small-molecule libraries with unique functionalities, implement high-throughput biology in annotated libraries, reconsider protein sciences and integrate sophisticated computational analyses, all to glean unexpected insights from biological systems. Examples include new types of therapeutic agent, such as targeted-protein degraders that link the cellular machinery of degradation to proteins of therapeutic interest, and reconsiderations of chemical equity, such as vast and chiral DNA-encoded libraries. We intend to organize around new types of chemical tool to make unprecedented insights into disease biology, and we expect that new therapeutic vectors will emanate immediately from these efforts ...
Posttranslational modifications (PTMs) orchestrate many vital events in cells, including the remodeling of chromatin in gene activation and inactivation, the transcription of active genes, the repair of damaged DNA, and the interaction of proteins in cellular signaling networks. Many enzymes are involved in putting these PTM marks in the right place at the right time, and in removing them in the proper context. Specific binder domains are involved in their recognition. Because of the consequences of their actions and because they can often be inhibited by small compounds, these proteins are often targets for drug development. With small compounds that act on these proteins we can, for instance, kill cancer cells, or influence signaling processes to reach a therapeutic outcome. This requires that we understand the actions of both the target proteins and the inhibitor substances to great detail in order for the therapeutic agents to be effective and safe.. We are interested to understand to atomic ...
This is a pretty good hit rate. Generally virtual screening campaigns are lucky to have a hit rate of a few percent. Curiously, the authors also found a similarly high hit rate during a past VS campaign against the well-known β2 adrenergic receptor. What could be responsible for this high hit rate against GPCRs? The reasons are interesting. One reason could be that GPCRs are very well adapted to bind small molecules in compact pockets, enclosing them and forming many kinds of productive interactions. But more intriguingly, as the authors have noted earlier, there is "biogenic bias" in favor of certain target-specific chemotypes in commercial libraries that are screened, both during VS as well as HTS. This in turn reflects the biases of medicinal chemists in picking and synthesizing certain kinds of chemotypes based on the importance of drug targets and past successes in hitting these targets. GPCRs clearly are enormously important, and GPCR-friendly ligand chemotypes thus constitute a large ...
The viral resistance of marketed antiviral drugs including the emergence of new viral resistance of the only marketed CCR5 entry inhibitor, maraviroc, makes it necessary to develop new CCR5 allosteric inhibitors. A mutagenesis/modeling approach was used (a) to remove the potential hERG liability in an otherwise very promising series of compounds and (b) to design a new class of compounds with an unique mutant fingerprint profile depending on residues in the N-terminus and the extracellular loop 2. On the basis of residues, which were identified by mutagenesis as key interaction sites, binding modes of compounds were derived and utilized for compound design in a prospective manner. The compounds were then synthesized, and in vitro evaluation not only showed that they had good antiviral potency but also fulfilled the requirement of low hERG inhibition, a criterion necessary because a potential approved drug would be administered chronically. This work utilized an interdisciplinary approach ...
Countless therapeutics - and certainly our earliest ones - were discovered from natural sources. Lodo Therapeutics, a new small molecule drug discovery startup based in New York City, is basing its platform on this premise: It will develop medicines that can be produced by uncultured soil bacteria and the human microbiome, chasing global health indications like tuberculosis.. The company just raised $17 million from a pool of high profile investors - most notably, the Bill and Melinda Gates Foundation, which has sponsored the underlying research for the company since 2014.. This research comes from the labs of cofounder Dr. Sean Brady, head of The Rockefeller Universitys Laboratory of Genetically Encoded Small Molecules. He posits:. ...
The long-term goal of this research project is to develop critically-needed small molecule drugs to help treat the approximately 34 million people worldwide living with HIV. The emergence of deleterious drug-resistance mutations against currently-approved therapies, such as the peptide drug T20, necessitates new strategies for targeting HIV life-cycle events that include complementary inhibition mechanisms and exploitation of regions with high sequence conservation. An innovative approach, recently developed in our lab, aims to leverage the wealth of energetic and structural information inherent to atomic-level molecular footprints - defined as per-residue interaction patterns within targetable pockets on proteins - to rationally identify, develop, and design novel small molecule inhibitors against the viral protein gp41. Our objectives in this project are to exploit the information contained in footprints to rationally design small molecules that specifically bind to gp41, inhibit membrane ...
About Neuralstem. Neuralstems patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system (CNS) diseases and conditions.. Neuralstems technology enables the discovery of small molecule compounds by systematic screening of chemical compounds against its proprietary human hippocampal stem cell line. The screening process has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brains capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central and peripheral nervous system conditions.. The company has completed Phase 1a and 1b studies evaluating NSI-189, a novel neurogenic small molecule product candidate, for the treatment of major depressive disorder or MDD, and is currently conducting a Phase 2 efficacy study for MDD.. Neuralstems stem cell therapy product candidate, ...
We believe HMPL-523 is a potential global first-in-class oral inhibitor targeting spleen tyrosine kinase (Syk), a key protein involved in B-cell signaling. Modulation of the B-cell signaling system has been proven to significantly advance the treatment of certain chronic immune diseases, such as rheumatoid arthritis as well as hematological cancers. To date, only monoclonal antibody immune modulators, which seek to use the patients own immune system to treat the disease, have been approved. As an oral drug candidate, we believe HMPL-523 has important advantages over intravenous monoclonal antibody immune modulators in rheumatoid arthritis in that as small molecule compounds clear the system faster, thereby reducing the risk of infections from sustained suppression of the immune system.. Moreover, other drug development companies have tried to design small molecule Syk inhibitors for the treatment of chronic immune diseases. However, designing an efficacious and safe Syk inhibitor for a major ...
THE seniors of Ambassador Prestwick kept up their rich vein of form when they beat Paisley 64-50 at home to go joint top of their section with Lanarkshire.
Helsinn Therapeutics (Helsinn) in the US is developing a series of small molecule compounds, called the NSAC compounds, which belong to a class of growth
Currently, we do not have any vacancies, but we are always interested to meet enthusiastic talent !. Interested?. Mail your motivation letter, together with your CV in English to Marco de Boer ([email protected]).. Company profile. NTrans Technologies BV was founded in 2015 based on a proprietary platform technology for the intracellular delivery of bioactive molecules developed at the Hubrecht Institute of the Royal Netherlands Academy of Sciences. The iTOP intracellular delivery technology is based on a combination of small molecule compounds which forces the uptake of large gulps of extracellular fluid (containing the bioactive molecules) by the cell (DAstolfo et al. 2015, Cell 161: 674-690). Once inside, the vesicles release their content into the cytoplasm, where the bioactive molecules (like gene editing systems) can exert their therapeutic action.. The goal of NTrans Technologies is to further develop the iTOP transduction technology into a therapeutic platform for the ...
Enobia Pharma (formerly BioMep) was engaged in a research programme focusing on the discovery and development of orally bioavailable, small molecule compounds
The absence of effective therapeutics against Alzheimers disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise
Recent insights into the pathophysiology of psoriasis have led to the identification of putative targets for pharmacological intervention. With the investigation for small molecule compounds that can...
Our lab is particularly interested in identifying novel host machineries that regulate viral life cycle and contribute to viral pathogenesis, and further investigating the molecular mechanisms underlining their functions. To achieve this goal, we are developing and employing cutting-edge systematic approaches, including proteomic and functional genomic tools, to unbiasedly identify previously unappreciated host genes that regulate viral transcription, transition of latency and reactivation, and viral oncogenesis for HIV and herpesviruses. Novel host genes are further studied thoroughly in our lab using classic approaches of virology, cellular and molecular biology. The long-term goal of our lab is to comprehensively study host-virus relationships at multiple levels (genetically, biochemically, and serologically), as well as to improve these studies with more quantitative, dynamic and in vivo settings. Small-molecule compounds targeting key host machineries are also under development for ...
An awful lot of drug discovery comes down (sooner or later) to screening compound collections. This has been true for a long time now, and it doesnt look like its going away, either. So with that in mind, whats in your collection? Did you buy a bunch of stuff from the vendors to fill it out? If so, your chemical
Harris MT, Walker DM, Drew ME, Mitchell WG, Dao K, Schroeder CE, Flaherty DP, Weiner WS, Golden JE, Morris JC. Interrogating a Hexokinase-Selected Small-Molecule Library for Inhibitors of Plasmodium falciparum Hexokinase. Antimicrobial Agents and Chemotherapy. 2013 ;57:3731-3737. ...
Wnt signaling is a branch of a functional network involved in a broad range of biological processes, such as development and homeostasis. It is one of the fundamental oncogenic pathways, and is implicated in multiple cancers. Thus targeting this pathway is an attractive therapeutic approach. Within the framework of biology oriented synthesis (BIOS), screening of the natural product inspired withanolide-based compound collection revealed potent inhibitors of Wnt signaling (IC50 = 100 nM) in human colorectal cancer cells. An assortment of different biochemical, cell biological and proteomic methods-based primary and secondary assays, were used to validate the bioactivity of our „lead compound" in the Wnt pathway. Our efforts towards identification of the compounds target protein will be discussed. Through a similar approach in a parallel project, a potent and selective small molecule inhibitor of cytokinesis was identified and validated.. ...
In this prospective, single-centre, double blind (within each cohort), placebo controlled, randomised study, safety and tolerability of PP-001 eye drops is assessed in healthy, adult volunteers. PP-001 is a novel small molecule inhibitor of Dihydroorotate Dehydrogenase (DHODH) with anti-inflammatory properties. PP-001 eye drops will be administered up to 4 times per day over a period of 13 days in ascending doses. Participants will be monitored for safety and tolerability evaluation of the study drug ...
Molecules that can covalently bind to a target have been typically excluded from compound libraries and treated as toxic or PAINS. Appearance on the market of drugs with a covalent mechanism of action has initiated revision of this "orthodox" paradigm. We have selected several sets of REAL covalent binders that involve popular warheads: sulfonyl fluoride, acrylamide, and boronic acid. For each warhead class, we provide a couple of sets. The first one contains molecules that comply with "rule of 5" and Veber criteria: MW≤500, SlogP≤5, HBA≤10, HBD≤5, rotatable bonds≤10, and TPSA≤140. The second set comprises fragments meeting "rule of 3" criteria: MW,300, SlogP≤3, HBA≤3, HBD≤3, rotatable bonds≤3, and TPSA≤60.. ...
Selleck provides signaling inhibitors, modulators and compound libraries with terrific validation, customer reviews, product citations, tech support and prompt delivery.
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download: small compounds taken from such dynamics and their P as maximal house networks. Wolber G, Dornhofer A, Langer T. Efficient snowed of First Microbial halides implementing previous rates. Schneidman-Duhovny D, Dror O, Inbar Y, Nussinov R, Wolfson HJ.
3PO is a novel small-molecule inhibitor of the PFKFB3 isozyme, 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 μM)....Quality confirmed by NMR,HPLC & MS.
Cresset Blaze Advanced ligand-base virtual screening to dramatically increase your wet screening hit rate at a fraction of the cost biologically relevant large chemical databases virtual screen of 10 million structures just takes a few hours, or calculations can be run overnight. lead-like hits hit rates high 30%, diversity Blaze screen. electrostatic character and shape of known ligands to rapidly search large chemical collections for molecules with similar properties Increase the diversity of your projects leads and backups Jump into new areas of chemical space Find novel lead-like hits from known actives Replace peptides with non-peptides or steroids with non-steroids Achieve substantial improvements in the properties of your hits.
the unwanted migration of regulatory T cells to the site of a tumor. About FLX475 FLX475 is a best-in-class oral, small molecule antagonist of CCR4. ...
Highlights DOI: 10.1002/anie.200500721 Drug Research Cellular Profiling of Small-Molecule Bioactivities: an Alternative Tool for Chemical Biology** Thorsten Berg* Keywords: fluorescent probes · inhibitors · phenotypic screening · proteins · signal transduction O ne of the main goals of chemical biology is to identify cell-permeable organic molecules that interfere with protein function to provide the scientific community with novel research tools for the investigation of biological questions.[1] There are currently two major approaches for the primary screening of chemical libraries to identify such bioactive organic molecules. In the first approach, inhibitors or activators of purified proteins or reconstituted, narrowly defined signaling pathways are sought in vitro. In the second approach, cells or organisms are treated with small molecules; those compounds which cause a desired phenotype are selected. The success of research projects that begin with such a phenotypic screen is dependent ...
COVID-19 poses a serious threat to peoples health, and it is urgent to develop drugs to treat COVID-19 quickly. The screening of anti-COVID-19 drugs by using the clinical and approved compounds can greatly shorten the research and development cycle. In addition, the virtual screening technology can effectively narrow the scope of screening and improve the screening efficiency in the pre-screening of new drugs.. Taking advantage of our virtual screening, we conduct virtual screening of approved compound library and clinical compound library based on the 3CL protease (PDB ID: 6LU7), Spike Glycoprotein (PDB ID: 6VSB), NSP15 (PDB ID: 6VWW), RDRP, PLPro and ACE2 (Angiotensin Converting Enzyme 2) structure. We design a unique collection of 1553 compounds which may have anti-COVID-19 activity. Anti-COVID-19 Compound Library will be a powerful tool for screening new anti-COVID-19 activity drugs.. ...
My research field is Phytochemistry; the investigation of the chemical constituents of plants. Working in a Department of Pharmacy, I am naturally interested in the plant kingdom as a rich source of novel, biologically active chemicals which may be useful medicinal agents in their own right, new chemical tools for biological research or lead compounds for medicinal chemistry research. Wherever possible, I collaborate with workers in other disciplines whose interests lie in the biological activities of these compounds; biologists, biochemists, clinicians and scientists in the pharmaceutical industry.. ...
Structure of PvdQ bound to HTS hit compound 3. (A)Electron density is shown, calculated with coefficients of the formFo-Fc generated prior to building the ligan
Research into the chemical biology of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including
Wang YS, Strickland C, Voigt JH, Kennedy ME, Beyer BM, Senior MM, Smith EM, Nechuta TL, Madison VS, Czarniecki M, McKittrick BA, Stamford AW, Parker EM, Hunter JC, Greenlee WJ, Wyss DF. Application of fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design to identify novel microM leads for the development of nM BACE-1 (beta-site APP cleaving enzyme 1) inhibitors ...
Generating drugs can be a tricky and expensive home business. Although companies are spending exorbitant amounts on clinical trials, they currently have spent important time and money prior to to identify the best drug candidates for their trials. With its … Continue reading →. ...
Australian researchers have developed the first potent new small-molecule inhibitors capable of blocking the activation of apoptotic cell death before it causes damage to mitochondria, they reported in a study published in the Oct. 7, 2019, issue of Nature Chemical Biology. Those first-in-class inhibitors will be useful tools for evaluating the mechanisms underlying apoptosis, assessing the impact of the pharmacological blockade of apoptosis in experimental models and potentially have multiple clinical indications.
Evotec and IntelliCyt describe how primary-cell-based screening can generate multivariate activity profiles for potential immunotherapeutic agents.
提供693种凋亡相关化合物集合,靶向作用于Bcl-2,Caspase,p53,TNF-alpha,Mdm2,survin等,可用于高通量筛选和高内涵筛选。
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months ...
BioAssay record AID 463095 submitted by Burnham Center for Chemical Genomics: Confirmation of uHTS identification of small molecules that induce b-cell replication in the MIN-6 cell line.
The Small Molecules News Channel provides a listing of specific press releases about new chemical entities (NCE) or small molecules
The Small Molecules News Channel provides a listing of specific press releases about new chemical entities (NCE) or small molecules
Heres an interesting article from a former colleague of mine, Pat Walters, on virtual chemical libraries. Those, of course, are meant to fill in the (large,
We offer comprehensive support in developing your hit compounds. Naturally such programs are realised most efficiently when biological actives originate from our screening collection. However, even if the hit compounds are from the collections of other vendors lead identification and optimization projects can proceed most productively in our hands. Sometimes for this we only need to synthesize first examples of the given chemical series and validate synthesis route.. ...
Protein Targeting with Small Molecules von Hiroyuki Osada und Buchbewertungen gibt es auf ReadRate.com. Bücher können hier direkt online erworben werden.
Another study identified potential drug targets for three neurological 価格 INNO-406 disorders Alzheimers disease, Parkinsons disease and Schizo phrenia. This st
LDN193189 is a highly potent and selective BMP pathway inhibitor specifically targeting ALK2 (IC50=5 nM) and ALK3 (IC50=30 nM) receptors and only weakly inhibiting ALK4, ALK5, and ALK7. ESIBIO.com.
টক্সিন" ( প্রাচীন গ্রিক: শব্দτοξικόν toxikon(টক্সিকন) থেকে এর উৎপত্তি) হচ্ছে এক প্রকার বিষাক্ত পদার্থ যা উৎপন্ন হয় জীব বা জীবকোষের অভ্যন্তরে।[১][২] টক্সিকেন্ট কৃত্রিমভাবে জীবকোষের বাইরে প্রস্তুত করা যায়। এই কাজটি প্রথম করেন জৈব রসায়নবিদ লুডউইক ব্রেইজের।(১৮৪৯-১৯১৯)[৩] টক্সিন হতে পারে small molecule, পেপটাইড অথবা প্রোটিন। এগুলো রোগ তৈরী করতে, শরীরের টিস্যুকে ধ্বংস করে দিতে সক্ষম। জৈব macromolecule ...
what do those of you do that do HIT cardio. I am going into my cutting phase next week, and am looking to get in some good cardio.
מידע אודות דר אריאל בניס, הפקולטה לניהול טכנולוגיה במכון הטכנולוגי חולון HIT
HIT יום פתוח בהנדסת חשמל ואלקטרוניקה - תואר שני - אירועים במכון טכנולוגי חולון
The histone lysine methyltransferase nuclear receptor-binding SET domain protein 2 (NSD2, also known as WHSC1/MMSET) is an epigenetic modifier and thought to play a driving role in oncogenesis. Both NSD2 overexpression and point mutations that increase its catalytic activity are associated with several human cancers. While NSD2 is an attractive therapeutic target, no potent, selective, and bioactive small molecule inhibitors of NSD2 have been reported to date, possibly due to the challenges of developing high-throughput assays for NSD2. Here, to establish a platform for the discovery and development of selective NSD2 inhibitors, we optimized and implemented multiple assays. We performed quantitative high-throughput screening with full-length wild-type NSD2 and a nucleosome substrate against a diverse collection of bioactive small molecules comprising 16,251 compounds. We further interrogated 174 inhibitory compounds identified in the primary screen with orthogonal and counter assays and with ...
Novartis Institutes for BioMedical Research, Cambridge, USA. Affinity proteomics and target identification for small molecule drug candidates. Affinity proteomics has become a valuable tool in preclinical small molecule drug discovery, in particular in the context of target identification and elucidation of the mechanism of action for drug candidates from phenotypic and pathway-centric approaches to drug discovery. Quantitative chemoproteomics, employing variations of a competition-based approach to small molecule affinity chromatography and mass spectrometry-based protein identification and quantitation, identifies cellular protein interactors and thus potential targets of drug candidates under conditions approximating the disease-relevant in vivo situation. Several examples will be presented and discussed in the context of orthogonal approaches to the generation of target hypotheses. On the other hand, the identification of protein-protein interactions using e.g. an affinity-tagged bait ...
Current Research and Scholarly Interests We are interested in the structure, dynamics and function of eukaryotic transport proteins mediating ions and major nutrients crossing the membrane, the kinetics and regulation of transport processes, the catalytic mechanism of membrane embedded enzymes and the development of small molecule modulators based on the structure and function of membrane proteins. ...
0009]These same Rho kinase inhibitors are cell permeable, and cause changes in cytoskeletal function and cell behavior consistent with loss of Rho kinase activity, similar to effects of the trans-dominant inhibitory mutants. Effects have been observed both in cultured cells in vitro and in physiologically responsive tissues in vivo [Nagumo, H. et al., 2000, Am J Physiol Cell Physiol. 278:C57-C65; Sinnett-Smith, J. et al., 2001, Exp Cell Res. 266:292-302; Chrissobolis, S. and Sobey, C. G., 2001, Circ Res. 88:774-779; Honjo, M. et al., 2001, Invest Ophthalmol Vis Sci. 42:137-144; Takahara, A. et al., 2003, Eur J Pharmacol. 460:51-57; Fournier, A. E. et al., 2003, J Neurosci. 23:1416-1423; Rikitake, Y. et al., 2005, Stroke. 36:2251-2257; Slotta, J. E. et al. 2006, Inflamm Res. 55:364-367; Ying, H. et al., 2006, Mol Cancer Ther. 5:2158-2164]. The correlation between small molecule inhibition of Rho kinases and changes in cell behavior both in vitro and in vivo (e.g., vascular smooth muscle ...
Discussions of therapeutic suppression of hedgehog (Hh) signaling almost exclusively focus on receptor antagonism; however, hedgehogs biosynthesis represents a unique and potentially targetable aspect of this oncogenic signaling pathway. Here, we review a key biosynthetic step called cholesterolysis from the perspectives of structure/function and small molecule inhibition. Cholesterolysis, also called cholesteroylation, generates cholesterol-modified Hh ligand via autoprocessing of a hedgehog precursor protein. Post-translational modification by cholesterol appears to be restricted to proteins in the hedgehog family. The transformation is essential for Hh biological activity and upstream of signaling events. Despite its decisive role in generating ligand, cholesterolysis remains conspicuously unexplored as a therapeutic target.
Flavia Amadeu de Oliveira, Ph.D.. "I am pleased and delighted for being the recipient of ASBMR Fund for Research and Education Research Grant 2019. I am currently investigating the molecular targets driving osteosarcoma metastasis, focusing specifically on FGFR and mTOR signalling. My work has so far demonstrated that small molecule inhibition of these pathways could serve as a potential therapy for inhibiting metastasis in osteosarcoma patients. The transcriptional and biochemical mechanisms underlying this effect are not known and therefore this award will help me to take a global approach through analysing and bridging together large genomic and proteomic data sets. Well-established training courses will provide me with additional expertise which I will be using for current and future research projects with a liberty to analyse data based on my independent biological questions. This award will be used in part to obtain bulk RNA-seq and proteomic data of tumour cells excised from different ...
Poly-α2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. We report that cell surface PSA expression can be reversibly inhibited by a small molecule,N-butanoylmannosamine (ManBut). Inhibition occurs through a metabolic mechanism in which ManBut is converted to unnatural sialic acid derivatives that effectively act as chain terminators during cellular PSA biosynthesis. N-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events. ...
BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing |160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with
1. Lineage specific transcription factors.. We are using genetic and biochemical approaches to define the molecular mechanisms through which lineage-specific transcriptional regulators orchestrate self-renewal and differentiation, focussing on SOX, FOX and bHLH families. These lie at the heart of cell fate decision-making by neural stem and progenitor cells during development and within brain tumours.. 2. Chemical and genetic screening. We are carrying out image-based small molecule screens to search for new agents and pathways that can modulate self-renewal and differentiation of normal and glioblastoma-derived neural stem cells. 3. Epigenetic programming and reprogramming. We are investigating whether changes to the epigenome within glioblastoma-derived cancer stem cells enable suppression of malignant properties. We are using both direct differentiation as well as nuclear reprogramming strategies to test this.. 4. Genome editing. Designer transcription factors and nucleases (TALENs or ...
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0031]The procedure for molecular docking involves: 1) selection of structural pockets in PKCiota suitable for interactions with drug-like small compounds, and 2) molecular docking simulations where each one of approximately 300,000 small compounds (MW,500) is positioned in the selected structural pocket and scored based on predicted polar (e.g., H bond) and non-polar (e.g. Van der Waals) interactions. The top 30 scoring compounds for each selected structural pocket were obtained for use in functional assays. Docking calculations were performed with the Oct. 15, 2002 development version of DOCKv5.1.0. molecular docking calculations The coordinates for the crystal structure PKC, PDB code 1ZRZ, was used. The molecular surface of the structure was explored using sets of spheres to describe potential binding pockets. The spheres literally fill in the available pocket spaces where a ligand might be able to form a complex. DOCK uses the spheres as a guide to search for orientations of each compound ...
With more than 10 years of accumulation, KBP has built a small molecule compound library with over 3,000,000 chemical compounds consisting of compounds designed and synthesized by KBP with unique chemical structures and high potency, compounds synthesized based on different core structures that cover almost all known core structures, and a natural product library of compounds extracted from plants, marine organisms and microorganisms.. Coupled with our bio-evaluation technology platform, the compound library enables KBP to identify and progress unique drugs that fit global unmet medical need quickly and efficiently.. Over 100 lead compounds have been screened from the library, and 3 compounds have entered into international clinical development.. ...
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The Wnt/ß-catenin signaling pathway controls important cellular events during development and often contributes to disease when dysregulated. Using high throughput screening we have identified a new small molecule inhibitor of Wnt/ß-catenin signaling, WIKI4. WIKI4 inhibits expression of ß-catenin target genes and cellular responses to Wnt/ß-catenin signaling in cancer cell lines as well as in human embryonic stem cells. Furthermore, we demonstrate that WIKI4 mediates its effects on Wnt/ß-catenin signaling by inhibiting the enzymatic activity of TNKS2, a regulator of AXIN ubiquitylation and degradation. While TNKS has previously been shown to be the target of small molecule inhibitors of Wnt/ß-catenin signaling, WIKI4 is structurally distinct from previously identified TNKS inhibitors.