Small Molecule Libraries
Combinatorial Chemistry Techniques
High-Throughput Screening Assays
Drug Evaluation, Preclinical
Molecular Structure
Gene Library
Libraries, Medical
High-throughput synthesis and screening of cyclic peptide antibiotics. (1/1231)
Cyclic peptides are a rich source of biologically active compounds and are produced in nature by plants, bacteria, fungi, and lower sea animals. A high-throughput methodology has been developed for the combinatorial synthesis, screening, and identification of cyclic peptide natural product analogues with improved biological activities or useful new activities. The methodology was applied to generate a library of 1716 tyrocidine A analogues, which were screened for antibacterial activity in 96-well plates. The identity of the active peptides was determined by partial Edman degradation/mass spectrometry. This has resulted in the discovery of a series of tyrocidine analogues that have significantly improved therapeutic indices compared to the natural product. The availability of tyrocidine analogues with varying antibacterial activities has provided important insights into the structure-function relationship of tyrocidine A, which should help reveal its mechanism of action. (+info)Antibacterial targets in fatty acid biosynthesis. (2/1231)
The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for the development of new antibacterial agents. The extended use of the antituberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for antibacterial development. Differences in subcellular organization of the bacterial and eukaryotic multienzyme fatty acid synthase systems offer the prospect of inhibitors with host versus target specificity. Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential. An almost complete catalog of crystal structures for the enzymes of the type II fatty acid biosynthesis pathway can now be exploited in the rational design of new inhibitors, as well as the recently published crystal structures of type I FAS complexes. (+info)The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen. (3/1231)
To identify the pharmacophore of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen (PSMA), a small analog library was designed and screened for inhibitory potency against PSMA. The design of the lead inhibitor was based upon N-acyl derivatives of endogenous substrate folyl-gamma-Glu and incorporates a phosphoramidate group to interact with the PSMA catalytic zinc atoms. The scope of the analog library was designed to test the importance of various functional groups to the inhibitory potency of the lead phosphoramidate. The IC(50) for the lead phosphoramidate inhibitor was 35 nM while the IC(50) values for the analog library presented a range from 0.86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. (+info)Evolutionary conservation of drug action on lipoprotein metabolism-related targets. (4/1231)
Genetic analysis has shown that the slower than normal rhythmic defecation behavior of the clk-1 mutants of Caenorhabditis elegans is the result of altered lipoprotein metabolism. We show here that this phenotype can be suppressed by drugs that affect lipoprotein metabolism, including drugs that affect HMG-CoA reductase activity, reverse cholesterol transport, or HDL levels. These pharmacological effects are highly specific, as these drugs affect defecation only in clk-1 mutants and not in the wild-type and do not affect other behaviors of the mutants. Furthermore, drugs that affect processes not directly related to lipid metabolism show no or minimal activity. Based on these findings, we carried out a compound screen that identified 190 novel molecules that are active on clk-1 mutants, 15 of which also specifically decrease the secretion of apolipoprotein B (apoB) from HepG2 hepatoma cells. The other 175 compounds are potentially active on lipid-related processes that cannot be targeted in cell culture. One compound, CHGN005, was tested and found to be active at reducing apoB secretion in intestinal Caco-2 cells as well as in HepG2 cells. This compound was also tested in a mouse model of dyslipidemia and found to decrease plasma cholesterol and triglyceride levels. Thus, target processes for pharmacological intervention on lipoprotein synthesis, transport, and metabolism are conserved between nematodes and vertebrates, which allows the use of C. elegans for drug discovery. (+info)Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation. (5/1231)
BACKGROUND AND PURPOSE: Glycogen synthase kinase-3 (GSK-3) affects neuropathological events associated with Alzheimers disease (AD) such as hyperphosphorylation of the protein, tau. GSK-3beta expression, enzyme activity and tau phosphorylated at AD-relevant epitopes are elevated in juvenile rodent brains. Here, we assess five GSK-3beta inhibitors and lithium in lowering phosphorylated tau (p-tau) and GSK-3beta enzyme activity levels in 12-day old postnatal rats. EXPERIMENTAL APPROACH: Brain levels of inhibitors following treatment in vivo were optimized based on pharmacokinetic data. At optimal doses, p-tau (Ser(396)) levels in brain tissue was measured by immunoblotting and correlated with GSK-3beta enzyme activities in the same tissues. Effects of GSK inhibitors on p-tau, GSK-3beta activities and cell death were measured in a human neuronal cell line (LUHMES). KEY RESULTS: Lithium and CHIR98014 reduced tau phosphorylation (Ser(396)) in the cortex and hippocampus of postnatal rats, while Alsterpaullone and SB216763 were effective only in hippocampus. AR-A014418 and Indirubin-3'-monoxime were ineffective in either brain region. Inhibition of p-tau in brain required several-fold higher levels of GSK inhibitors than the IC(50) values obtained in recombinant or cell-based GSK-3beta enzyme activity assays. The inhibitory effect on GSK-3beta activity ex vivo correlated with protection against cell death and decrease of p-tau- in LUHMES cells, using low microM inhibitor concentrations. CONCLUSIONS AND IMPLICATIONS: Selective small-molecule inhibitors of GSK-3 reduce tau phosphorylation in vivo. These findings corroborate earlier suggestions that GSK-3beta may be an attractive target for disease-modification in AD and related conditions where tau phosphorylation is believed to contribute to disease pathogenesis. (+info)High-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias. (6/1231)
Fatty acids are implicated in the development of dyslipidemias, leading to type 2 diabetes and cardiovascular disease. We used a standardized small compound library to screen humanized yeast to identify compounds that inhibit fatty acid transport protein (FATP)-mediated fatty acid uptake into cells. This screening procedure used live yeast cells expressing human FATP2 to identify small compounds that reduced the import of a fluorescent fatty acid analog, 4,4-difluoro-5-methyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoic acid (C(1)-BODIPY-C(12)). The library used consisted of 2,080 compounds with known biological activities. Of these, approximately 1.8% reduced cell-associated C(1)-BODIPY-C(12) fluorescence and were selected as potential inhibitors of human FATP2-mediated fatty acid uptake. Based on secondary screens, 28 compounds were selected as potential fatty acid uptake inhibitors. Some compounds fell into four groups with similar structural features. The largest group was structurally related to a family of tricyclic, phenothiazine-derived drugs used to treat schizophrenia and related psychiatric disorders, which are also known to cause metabolic side effects, including hypertriglyceridemia. Potential hit compounds were studied for specificity of interaction with human FATP and efficacy in human Caco-2 cells. This study validates this screening system as useful to assess the impact of drugs in preclinical screening for fatty acid uptake. (+info)Inhibition of monometalated methionine aminopeptidase: inhibitor discovery and crystallographic analysis. (7/1231)
Two divalent metal ions are commonly seen in the active-site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high-throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase. (+info)A class of small molecules that inhibit TNFalpha-induced survival and death pathways via prevention of interactions between TNFalphaRI, TRADD, and RIP1. (8/1231)
Small-molecule library screening to find compounds that inhibit TNFalpha-induced, but not interleukin 1beta (IL-1beta)-induced, intercellular adhesion molecule 1 (ICAM-1) expression in lung epithelial cells identified a class of triazoloquinoxalines. These compounds not only inhibited the TNFalpha-induced nuclear factor kappaB (NFkappaB) survival pathway but also blocked death-pathway activation. Such dual activity makes them unique against other known NFkappaB-pathway inhibitors that inhibit only a subset of TNFalpha signals leading to increased TNFalpha-induced cytotoxicity. Interestingly, these compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation. Further study showed that they blocked ligand-dependent internalization of the TNFalpha-TNFalphaR complex, thereby inhibiting most of the TNFalpha-induced cellular responses. Thus, compounds with a triazoloquinoxaline scaffold could be a valuable tool to investigate small molecule-based anti-TNFalpha therapies. (+info)A Small Molecule Library is a collection of a large number of chemically synthesized, low molecular weight (typically under 900 daltons) compounds, which are used in drug discovery and development research. These libraries contain diverse structures and chemical properties, allowing researchers to screen them against specific targets, such as proteins or genes, to identify potential lead compounds that can be further optimized for therapeutic use. The use of small molecule libraries enables high-throughput screening, which is a rapid and efficient method to identify potential drug candidates.
Combinatorial chemistry techniques are a group of methods used in the field of chemistry to synthesize and optimize large libraries of chemical compounds in a rapid and efficient manner. These techniques involve the systematic combination of different building blocks, or reagents, in various arrangements to generate a diverse array of molecules. This approach allows chemists to quickly explore a wide chemical space and identify potential lead compounds for drug discovery, materials science, and other applications.
There are several common combinatorial chemistry techniques, including:
1. **Split-Pool Synthesis:** In this method, a large collection of starting materials is divided into smaller groups, and each group undergoes a series of chemical reactions with different reagents. The resulting products from each group are then pooled together and redistributed for additional rounds of reactions. This process creates a vast number of unique compounds through the iterative combination of building blocks.
2. **Parallel Synthesis:** In parallel synthesis, multiple reactions are carried out simultaneously in separate reaction vessels. Each vessel contains a distinct set of starting materials and reagents, allowing for the efficient generation of a series of related compounds. This method is particularly useful when exploring structure-activity relationships (SAR) or optimizing lead compounds.
3. **Encoded Libraries:** To facilitate the rapid identification of active compounds within large libraries, encoded library techniques incorporate unique tags or barcodes into each molecule. These tags allow for the simultaneous synthesis and screening of compounds, as the identity of an active compound can be determined by decoding its corresponding tag.
4. **DNA-Encoded Libraries (DELs):** DELs are a specific type of encoded library that uses DNA molecules to encode and track chemical compounds. In this approach, each unique compound is linked to a distinct DNA sequence, enabling the rapid identification of active compounds through DNA sequencing techniques.
5. **Solid-Phase Synthesis:** This technique involves the attachment of starting materials to a solid support, such as beads or resins, allowing for the stepwise addition of reagents and building blocks. The solid support facilitates easy separation, purification, and screening of compounds, making it an ideal method for combinatorial chemistry applications.
Combinatorial chemistry techniques have revolutionized drug discovery and development by enabling the rapid synthesis, screening, and optimization of large libraries of chemical compounds. These methods continue to play a crucial role in modern medicinal chemistry and materials science research.
High-throughput screening (HTS) assays are a type of biochemical or cell-based assay that are designed to quickly and efficiently identify potential hits or active compounds from large libraries of chemicals or biological molecules. In HTS, automated equipment is used to perform the assay in a parallel or high-throughput format, allowing for the screening of thousands to millions of compounds in a relatively short period of time.
HTS assays typically involve the use of robotics, liquid handling systems, and detection technologies such as microplate readers, imagers, or flow cytometers. These assays are often used in drug discovery and development to identify lead compounds that modulate specific biological targets, such as enzymes, receptors, or ion channels.
HTS assays can be used to measure a variety of endpoints, including enzyme activity, binding affinity, cell viability, gene expression, and protein-protein interactions. The data generated from HTS assays are typically analyzed using statistical methods and bioinformatics tools to prioritize and optimize hit compounds for further development.
Overall, high-throughput screening assays are a powerful tool in modern drug discovery and development, enabling researchers to rapidly identify and characterize potential therapeutic agents with improved efficiency and accuracy.
Preclinical drug evaluation refers to a series of laboratory tests and studies conducted to determine the safety and effectiveness of a new drug before it is tested in humans. These studies typically involve experiments on cells and animals to evaluate the pharmacological properties, toxicity, and potential interactions with other substances. The goal of preclinical evaluation is to establish a reasonable level of safety and understanding of how the drug works, which helps inform the design and conduct of subsequent clinical trials in humans. It's important to note that while preclinical studies provide valuable information, they may not always predict how a drug will behave in human subjects.
Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.
A "gene library" is not a recognized term in medical genetics or molecular biology. However, the closest concept that might be referred to by this term is a "genomic library," which is a collection of DNA clones that represent the entire genetic material of an organism. These libraries are used for various research purposes, such as identifying and studying specific genes or gene functions.
Medical libraries are collections of resources that provide access to information related to the medical and healthcare fields. They serve as a vital tool for medical professionals, students, researchers, and patients seeking reliable and accurate health information. Medical libraries can be physical buildings or digital platforms that contain various types of materials, including:
1. Books: Medical textbooks, reference books, and monographs that cover various topics related to medicine, anatomy, physiology, pharmacology, pathology, and clinical specialties.
2. Journals: Print and electronic peer-reviewed journals that publish the latest research findings, clinical trials, and evidence-based practices in medicine.
3. Databases: Online resources that allow users to search for and access information on specific topics, such as PubMed, MEDLINE, CINAHL, and Cochrane Library.
4. Multimedia resources: Audio and video materials, such as lectures, webinars, podcasts, and instructional videos, that provide visual and auditory learning experiences.
5. Electronic resources: E-books, databases, and other digital materials that can be accessed remotely through computers, tablets, or smartphones.
6. Patient education materials: Brochures, pamphlets, and other resources that help patients understand their health conditions, treatments, and self-care strategies.
7. Archives and special collections: Rare books, historical documents, manuscripts, and artifacts related to the history of medicine and healthcare.
Medical libraries may be found in hospitals, medical schools, research institutions, and other healthcare settings. They are staffed by trained librarians and information specialists who provide assistance with locating, accessing, and evaluating information resources. Medical libraries play a critical role in supporting evidence-based medicine, continuing education, and patient care.
I'm sorry for any confusion, but "Libraries" is not a term that has a medical definition. A library is a collection of sources of information and similar resources, made accessible to a community for reference or borrowing. This can include books, magazines, audio visual materials, and digital resources. If you have any questions related to health or medicine, I'd be happy to try to help answer those!
Lumateperone
Ion chromatography
TRPC3
DNA-encoded chemical library
David R. Liu
Combinatorial chemistry
Approved Drug Products with Therapeutic Equivalence Evaluations
Melanin-concentrating hormone receptor 1
Plasminogen activator inhibitor-1
Stapled peptide
RNA-targeting small molecule drugs
EPH receptor A2
AOH1996
HVCN1
Split and pool synthesis
Elabela
Cheminformatics
Fukutin-related protein
Chemical biology
Marinella Mazzanti
Acadia Pharmaceuticals
Structural bioinformatics
Mass spectrometry
Systematic evolution of ligands by exponential enrichment
Peptide spectral library
ADARB1
Chemical similarity
PubChem
Small RNA sequencing
Chem-seq
Sima Lev
Ocular Diseases Small Molecules Library
Product Sheet Small Molecule Chemical Libraries
Strategies for developing DNA-encoded libraries beyond binding assays | Nature Chemistry
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment
User Center BioChemMall - The Library of Active Small Molecule
Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation | Nature...
"Strategies for the Synthesis of Glycosylated Small Molecule Libraries " by Zachary Cannone
Small molecules containing rigidified thiophenes and a cyanopyridone acceptor unit for solution-processable bulk-heterojunction...
Prestwick Original Molecules Library<...
Chemical Libraries: Screening for Biologically Active Small Molecules - CHEMICAL BIOLOGY
CARM1 Inhibitor The CARM1 Inhibitor controls the biological activity of CARM1. This small molecule/inhibitor is primarily used...
Wortmannin, (PI3 Kinase inhibitor) The Wortmannin, (PI3 Kinase inhibitor) controls the biological activity of PI3 Kinase. This...
Lumateperone - Wikipedia
Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment
High Throughput Screening: The Discovery of Bioactive Substances - John P. Devlin - Google Books
Description: Characterisation and differentiation of kinase binding pockets in PKA and PIM1 by small molecule fragments using...
MODULATING PROTEIN FUNCTION WITH SMALL MOLECULES THROUGH COMPUTATIONAL AND EXPERIMENTAL DESIGN TECHNIQUES
Assessing the stability of membrane proteins to detect ligand binding using differential static light scattering
Polyisocyanides As a New Alignment Medium To Measure Residual Dipolar Couplings for Small Organic Molecules | Organic Letters
Utilization of Lignin-Derived Small Molecules: Epoxy Polymers from Lignin Oxidation Products | ACS Applied Bio Materials
A screen of the NIH clinical collection small molecule library identifies potential anti-coronavirus drugs. - FLCCC | Front...
Molecules | Free Full-Text | Molecular Docking and Structure-Based Drug Design Strategies
Is there a future for small molecule drugs in the treatment of rheumatic diseases? - Zurich Open Repository and Archive
KNIME interfaces • Drug discovery workflows • BioSolveIT
Rempi spectroscopic studies of some small molecules in the gas-phase - ePrints Soton
Synthesis of Bioactive Molecules IV review
Small Molecule Drug Discovery Market 2022 - 2028: Remarkable Growth Factors That Is Changing the Course of Industry Over Coming...
Business & Industry News Channel
Signature-based small molecule screening identifies cytosine arabinoside as an EWS/FLI modulator in Ewing sarcoma. | Broad...
Compounds18
- Neri, D. & Lerner, R. A. DNA-encoded chemical libraries: a selection system based on endowing organic compounds with amplifiable information. (nature.com)
- Here, we explore this strategy using an anti-mutant RAS antibody fragment as a competitor in a small-molecule library screen for identifying RAS-binding compounds. (nih.gov)
- Our results may aid RAS-dependent cancer drug development and demonstrate a general concept for developing small compounds to replace intracellular antibody fragments, enabling rational drug development to target validated PPIs. (nih.gov)
- This Library is made of a collection of 344 original exclusive compounds representing your premium resource for novel screening hit discovery. (prestwickchemical.com)
- The large size of chemistry space compared with the library sizes that are feasible to screen requires careful selection of the compounds for the screening library to maximize screening success. (schoolbag.info)
- When in vitro biologic assays replaced in vivo animal models as the first tool to assess biologic activity of molecules in drug discovery, the possibility existed to test many more compounds than was possible before. (schoolbag.info)
- This triggered the hope that the slow process of lead discovery, which relies to a large extent on medical chemists' intuition and serendipity, could be accelerated by a systematic brute-force screening of large collections of chemical compounds, for which the term "chemical libraries" has been introduced. (schoolbag.info)
- Because only a small subset of the chemistry space can be screened, the compounds must be chosen appropriately to maximize the success of the screen. (schoolbag.info)
- Significant progress is being made, and methods for deconstructing lignin are producing good yields of small, mononuclear aromatic products-sufficient amounts to enable studies of the potential use of these compounds as replacements for compounds currently produced from petroleum. (acs.org)
- Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs. (covid19criticalcare.com)
- PURPOSE OF REVIEW: In this review, we outline the landscape of recent developments regarding small molecule compounds for the treatment of inflammatory disorders by discussing drug candidates currently in the pipeline. (uzh.ch)
- Over 250 billion tiny compounds may be found in X-libraries, Chem's a leader in DEL technology. (medgadget.com)
- The centre will use the library â both the actual compounds and an associated database â for screening activities to identify new drug candidates for infectious tropical diseases that affect people in poor countries. (worldpharmanews.com)
- 12 million commercially available small molecule compounds. (advion.com)
- In a single-well setup we used the reporter in HeLa cells to screen a small molecule library of 33 000 compounds. (cancerindex.org)
- ChemDiv's Factor XIa Targeted Library contains ~6,500 compounds. (chemdiv.com)
- 2. Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. (chemdiv.com)
- The small molecule collection, of around 200 thousand compounds, is distinguished by its novel and unique design concept of optimized chemical diversity. (enamine.net)
Inhibitors3
- RECENT FINDINGS: Regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors of a number of pathways are tested as new anti-inflammatory agents. (uzh.ch)
- This article reviews current anticancer small-molecule inhibitors targeting epigenetic modified enzymes and displays their performances in different stages of clinical trials. (frontiersin.org)
- In this review, we summarize the basic principles manipulating the abovementioned epigenetic pathways and highlight the evidence of the promising clinical and preclinical results using small-molecule inhibitors against chromatin regulators for cancer treatment. (frontiersin.org)
Ligands1
- In the absence of any knowledge, it is proposed to screen smaller ''lead-like'' ligands with preference. (schoolbag.info)
Proteins2
- Small-molecule controlled molecular systems also possess tremendous value in bioengineering and biomedical applications: activation of protein function allows the construction of protein switches and biosensor proteins, whereas inhibition of protein function contributes to the development of novel therapeutic agents. (ku.edu)
- Small-molecule medications that selectively eliminate RNAs encoding disease-causing proteins by bringing them close to nucleases make up this new family of targeted RNA degraders. (medgadget.com)
Targets5
- For the design of the screening library, we use emerging Targets: retinol-binding protein 4 (RBP4), factor D inhibition as alternative complement pathway, and VEGF pathway. (chemdiv.com)
- In this Perspective, we discuss the recent progress in using DNA-encoded chemical libraries to interrogate complex biological targets and their potential to identify structures that elicit function or possess other useful properties. (nature.com)
- Furnishing the latest interdisciplinary information on the most important and frequently the only investigational system available for discovery programs that address the effects of small molecules on newly discovered enzyme and receptor targets emanating from molecular biology, this timely resource facilitates the transition from classical to high throughput screening (HTS) systems and provides a solid foundation for the implementation and development of HTS in bio-based industries and associated academic environments. (google.com)
- We demonstrate that a gene expression-based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. (broadinstitute.org)
- One researcher in Singapore is developing probes in reverse, starting with synthesized fluorescent molecules and then finding the targets that they label. (acs.org)
Antibody3
- A potential solution to these problems is to select intracellular antibody fragments to block PPIs, use these antibody fragments for target validation in disease models and finally derive small molecules overlapping the antibody-binding site. (nih.gov)
- 6FA4: Antibody derived (Abd-7) small molecule binding to KRAS. (rcsb.org)
- An alpaca was immunized with a TBBPA hapten coupled to thyroglobulin and a variable domain of heavy chain antibody (VHH) T3-15 highly selective for TBBPA was isolated from a phage displayed VHH library using heterologous coating antigens. (cdc.gov)
Assay2
- A small-molecule library enriched for FDA-approved drugs was screened with a high-throughput, ligation-mediated amplification assay with a fluorescent, bead-based detection. (broadinstitute.org)
- To elucidate regulatory mechanisms governing the maintenance and propagation of human HSCs ex vivo, we screened libraries of annotated small molecules in human cord blood (CB) cells using an optimized assay for detection of functional HSCs during culture. (lu.se)
Identifies2
- A screen of the NIH clinical collection small molecule library identifies potential anti-coronavirus drugs. (covid19criticalcare.com)
- Signature-based small molecule screening identifies cytosine arabinoside as an EWS/FLI modulator in Ewing sarcoma. (broadinstitute.org)
Pathway2
- Lerner, R. A. & Brenner, S. DNA-encoded compound libraries as open source: a powerful pathway to new drugs. (nature.com)
- ESCAR has a design of two acceptor chambers representing the blood uptake pathway and the lymphatic uptake pathway, respectively, although only the blood uptake pathway was investigated for small molecules in this study. (ku.edu)
Synthesis2
- The synthesis of glycosylated small molecule compound libraries remains a difficult challenge in the field of organic chemistry. (uconn.edu)
- Course organizer Peter Spégel Center for Analysis and Synthesis Department of Chemistry Lund University course gives theoretical and practical knowledge on how mass spectrometry can be used in qualitative and quantitative analyses of small molecules. (lu.se)
Therapeutics1
- Small Molecule Therapeutics for Schizophrenia. (wikipedia.org)
Fragment2
- The primary aim of this thesis was the crystallographic analysis of PKA and Pim1 crystals in complex with small fragment-like molecules to identify potential fragment binders in the protein kinase binding pockets. (uni-marburg.de)
- Starting from a template small molecule or fragment in a PDB or proprietary x-ray structure, the user first defines a common element of the library (the unchanging core element), and then selects from a pre-installed list the chemical reaction that will create the library (e.g. a particular amide formation). (biosolveit.de)
Biological1
- On the other hand, we investigate how the biological molecules operate together, both in health and disease. (ucsf.edu)
Therapeutic1
- The library combines promising drug-like properties as well as favorable ADME-Tox properties with high potential therapeutic score. (prestwickchemical.com)
Enzyme2
- Biologists use them to stain specific cell types, biochemists rely on them to monitor enzyme activity, and analytical chemists use them to detect molecules in the environment. (acs.org)
- Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. (cancerindex.org)
Screening13
- Boder, E. T. & Wittrup, K. D. Yeast surface display for screening combinatorial polypeptide libraries. (nature.com)
- The screening of chemical libraries is one of the major sources for new leads in drug discovery. (schoolbag.info)
- In the screening process, physical high-throughput screening (HTS) can be combined with virtual screening either to avoid the high-throughput primary screen of the whole library or to limit false negatives by combining primary HTS and virtual screening results. (schoolbag.info)
- To enable the subsequent functional rescue, I used the removed structural elements as a template for ligand-based virtual screening and discovered a set of candidate small molecules that mimic the three-dimensional geometry and chemical properties of the removed chemical moieties. (ku.edu)
- Based on similarity, infiniSee finds molecules of interest in screening libraries or Chemical Spaces of almost infinite size. (biosolveit.de)
- Novo Nordisk will donate a licence to its small molecule compound library to the National Center for Drug Screening (NCDS) affiliated to Shanghai Institute of Materia Medica, Chinese Academy of Sciences. (worldpharmanews.com)
- Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. (broadinstitute.org)
- Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. (broadinstitute.org)
- We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application. (broadinstitute.org)
- Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries. (cancerindex.org)
- Under the agreement, Orion co-funded and supported the design and generation of the library containing a highly diverse collection of chemotypes for target-agnostic high throughput screening (HTS). (enamine.net)
- Michael Bossert, Head Strategic Alliances at Enamine, commented: "Our growing homemade screening libraries, the largest collection available in the world, constitute ideal starting points for any HTS and hit identification platform to spot possible beneficial effects against any of a large number of diseases. (enamine.net)
- Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine K D values. (lu.se)
Synthetic2
- The clandestine chemist has to switch their method of production according to the availability of different starting materials, thus a number of synthetic routes are available to a given drug molecule. (soci.org)
- On the one hand, we reduce biology to its molecular components, and seek to change how these fit together using synthetic molecules we design. (ucsf.edu)
Compound Library1
- For instance, in August 2022, BioDuro-Sundia and X-Chem announced jointly that DNA Encoded Compound Library (DEL) technology services will be made available in China to assist global pharma firms in finding new small molecule medications more swiftly. (medgadget.com)
Chemists1
- Dr J J Keating (University College Cork) is one of a small group of chemists who synthesise drugs of abuse such as, for example, MDMA (more commonly known as ecstasy) and want the world to know about it! (soci.org)
Chemistry3
- Although large pharmaceutical companies screen compound libraries in the magnitude of 10 6 molecules, this approach is far away from a systematic brute-force approach because the chemistry space is estimated to contain 10 13 -10 60 small molecules (1). (schoolbag.info)
- Leverage an industry-leading, integrated digital chemistry platform to explore vast chemical space efficiently and design better molecules in fewer design cycles. (schrodinger.com)
- I want to get the latest chemistry news from C&EN in my inbox every week. (acs.org)
Fragments3
- The fragments used for this study were extracted as a part of an in-house library comprising 361 entries. (uni-marburg.de)
- Remote binding fragments were analyzed in terms of the buried surface area with respect to the proximate PKA molecules to obtain some figures-of-merits, whether binding only occurs in the crystallographic packing and would turn out as 'artefacts' during an analysis by a method focussing on conditions in the solute phase. (uni-marburg.de)
- Five of these 15 fragments revealed a relatively high percentage of buried surface area with a neighbouring PKA molecule. (uni-marburg.de)
20221
- The market for small molecule drug discovery was estimated at US$ 43,571.6 Mn in 2021 and is anticipated to grow at a CAGR of 8.1% from 2022 to 2028 to reach US$ 74,672.5 Mn. (medgadget.com)
RNAs1
- Several other antisense RNAs as well as the more malleable small interfering RNA molecules ('-sirans') are currently in early-phase clinical trials. (medscape.com)
Organic1
- Extrapolation from a systematic enumeration of all theoretically viable organic molecules up to 11 non-H atom toward 25 non-H atoms (the average size of drug-like molecules) suggest the existence of 10 27 unique structures (3). (schoolbag.info)
Quantitative1
- By utilizing structural information obtained through X-ray crystallography or NMR spectroscopy, these tools allow efficient and affordable examination of large small-molecule databases and provide quantitative evaluation of the likelihood that a given protein-ligand interaction occurs. (ku.edu)
METHODS1
- Much effort has been invested in developing methods for producing small molecules from lignin as a way to source feedstock chemicals from renewable sources. (acs.org)
Assays1
- Yet, suitable high-throughput editing assays are needed to efficiently screen chemical libraries for modifiers of ADAR1 activity. (cancerindex.org)
Enables1
- The non-exclusive agreement enables Proteros to exclusively offer access to this high-quality non-redundant HTS library to all their clients. (enamine.net)
Drugs2
- Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered unsuitable for PPI inhibition. (nih.gov)
- Is there a future for small molecule drugs in the treatment of rheumatic diseases? (uzh.ch)
Molecular1
- Mass spectrometry for small molecules includes an overview of mass spectrometric techniques that can be used for analysis of low molecular weight analytes in both the gas and liquid phase. (lu.se)
Details1
- Please contact the current institution's library for further details. (bl.uk)
Design2
- When knowledge about the target is available, it can be used for target-focused compound selection or for library design. (schoolbag.info)
- BioSolveIT-FragXplorer is a virtual library builder and docking-workflow for drug design and discovery designed to explore binding sites MedChem-style. (biosolveit.de)
Inhibitor2
- This small molecule/inhibitor is primarily used for Cell Structure applications. (sigmaaldrich.com)
- This small molecule/inhibitor is primarily used for Biochemicals applications. (sigmaaldrich.com)
Inhibition1
- In parallel to these efforts I carried out studies aimed at inhibition of protein function, as exemplified by my project that uses small molecules to disrupt a protein-RNA interaction. (ku.edu)
Protein2
Optimal1
- All molecules have been designed to ensure optimal chemical diversity and are suitable for various structural modifications yielding analogs with promising IP positions. (prestwickchemical.com)
Cells4
- Overview of the Immune System The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. (msdmanuals.com)
- Our facilities provide the opportunity to study molecules, cells, organs and entire organisms. (lu.se)
- Mitochondria are small structures that produce energy in almost all of your cells. (medlineplus.gov)
- The unused oxygen and fuel molecules build up in the cells and cause damage. (medlineplus.gov)
Development4
- The expansion of the worldwide small molecule drug discovery market, however, is anticipated to be constrained by factors such the high cost of drug development and rigorous regulations. (medgadget.com)
- Over the course of the forecast period, an increase in research and development efforts by industry participants is anticipated to boost market expansion for small molecule drug discovery. (medgadget.com)
- The worldwide small molecule drug discovery market is anticipated to provide attractive development prospects due to the increase in demand for small molecule medications. (medgadget.com)
- Players in the small molecule drug discovery market should see considerable growth prospects as the number of contract research and development firms grows. (medgadget.com)
Amounts1
- Using this process, very small amounts of these nucleic acid molecules can be analyzed. (cdc.gov)
Studies1
- British Library EThOS: Studies in the spectroscopy of small molecules. (bl.uk)
Applications1
- Future work would be focused on further optimizing ESCAR and expanding its applications via assessing more types of molecules and formulations. (ku.edu)
Unique2
- Based on the unique FTrees-mapping images you will immediately see, how similar parts of two molecules match to each other. (biosolveit.de)
- The companies are engaging in a joint multi-target collaboration for early-stage drug discovery projects using Proteros' "High Hanging Fruit" Discovery Platform, and now have decided to combine their expertise to assemble a unique and chemically diverse small molecule library collection. (enamine.net)
Large1
- Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. (lu.se)