• Biological assays to test the cytotoxicity of the compound 1b combined with electroporation were performed to determine its potential for future medical applications in cancer treatment. (hindawi.com)
  • It has been proven that combining electroporation with chemotherapy potentiates the cytotoxicity of drugs when the drugs' efficacy is limited by its uptake in the cell [ 9 - 13 ]. (hindawi.com)
  • The search for targeted drugs for cancer treatment includes consideration of natural products, which may provide new opportunities for antitumor cytotoxicity as single agents or in combination therapy. (cancer.gov)
  • The ethanolic extracts of the plant were examined for the presence of bioactive components and their total flavonoid content, with focusing on quercetin detection using thin layer bioautography (TLB) and brine shrimp lethality assay (BSLA) for cytotoxicity. (who.int)
  • In 1969, Stähelin made the key decision to include a test system for immunosuppression into the general screening program at Sandoz for compounds and extracts. (wikipedia.org)
  • The former issue was often neglected prior to initiating drug discovery programmes while the latter was considered impossible because it was purported that antibodies were unsuitable to derive compounds. (cancer.gov)
  • This seemed much larger than would be expected for the range of space occupied by drug-like chemical compounds, estimated at 300 to 1000 Å2 [4, 5]. (cancer.gov)
  • We exploited the specific binding of the antibody fragment and were able to identify RAS-binding compounds in antibody-competition assays (illustrated in Fig.1). (cancer.gov)
  • Compounds of interest include not only classical "drug-like" organic small molecules, but also peptides, proteins, and other bioactive chemical classes. (cancer.gov)
  • This library represents a selection of drug-like compounds aimed at modulating protein-protein interaction (PPI) of β-catenin with different proteins involved in significant physiological processes. (chemdiv.com)
  • This one-day conference held on 1 July 2008, and sponsored by SCI, the RSC, and ICI brought together scientists from the Republic of Ireland and from Northern Ireland who have varied interests in drug discovery and development and a common interest in synthesis. (soci.org)
  • Terry Rabbitts is Professor of Molecular Immunology in the Centre for Cancer Drug Discovery, Institute of Cancer Research, Sutton, London, UK. (cancer.gov)
  • The latter discovery was important for us because it suggests that the antibody combining sites could generally be accessible for implementing the Abd technology approach to drug discovery. (cancer.gov)
  • Since the advent of molecular cloning, target based screening has become the norm in pharmaceutical drug discovery. (docksci.com)
  • issues that often frustrate the present target based drug discovery programs. (docksci.com)
  • 2012). However, many drug discovery efforts rely on screening to identify starting points for Medicinal Chemistry, and screening in vivo in most cases is not commercially or ethically viable. (docksci.com)
  • In order to limit the reliance on non-predictive animal models, screening strategies utilizing human pluripotent stem cells (hPSCs) are increasingly considered as resources for drug discovery. (docksci.com)
  • In the early phases of drug discovery, phenotypic assays can be used to further our knowledge of the disease process and to identify those end points that are most likely to translate to the clinic. (docksci.com)
  • The perspective by Dr. Swinney analyzes the phenotypic end points used in the discovery of new molecular entities that have resulted from phenotypic drug discovery efforts. (docksci.com)
  • Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. (medsci.org)
  • Nathanael Gray is the Krishnan-Shah Family Professor of Chemical and Systems Biology at Stanford, Co-Director of Cancer Drug Discovery Co-Leader of the Cancer Therapeutics Research Program, Member of Chem-H, and Program Leader for Small Molecule Drug Discovery for the Innovative Medicines Accelerator (IMA). (stanford.edu)
  • and discovery that sphingosine-1-phosphate receptor-1 (S1P1) is the pharmacologically relevant target of the immunosuppressant drug Fingomilod (FTY720) followed by the development of Siponimod (BAF312), which is currently used for the treatment of multiple sclerosis. (stanford.edu)
  • There, he has established a discovery chemistry group that focuses on developing first-in-class inhibitors for newly emerging biological targets, including resistant alleles of existing targets, as well as inhibitors of well-validated targets, such as Her3 and RAS, that have previously been considered recalcitrant to small molecule drug development. (stanford.edu)
  • The Molecular Targets Program (MTP) provides the focus and infrastructure that enables CCR investigators to pursue molecularly targeted drug discovery research by promoting an interdisciplinary, collaborative, team-oriented approach to identifying and validating potential cancer-pertinent targets. (cancer.gov)
  • EFMC would like to remind his efforts, joint with Henk Timmerman and Han van de Waterbeemd, to launch the successful series of EFMC Short Course in Medicinal Chemistry in 2009 with a very successful course on "Improving Compound Quality: Physical Chemistry and DMPK Properties in Drug Discovery. (efmc.info)
  • Untargeted Metabolomics Study of the In Vitro Anti-Hepatoma Effect of Saikosaponin d in Combination with NRP-1 Knockdown. (cancer-genetics.org)
  • Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo . (frontiersin.org)
  • We used VES and FBZ, at low concentrations, singly and in combination, to test their inhibitory effects on proliferation of human and mouse prostate cancer cells in vitro. (researchgate.net)
  • Scientific Methods: In vitro growth inhibition assays were completed with AHCC alone and in combination with PLD in panel of human cancer cell lines and findings confirmed in vivo in an ovarian cancer xenograft mouse model. (researchgate.net)
  • Major Findings: The in vitro growth inhibition assays demonstrated additive activity when AHCC is co-administered with PLD. (researchgate.net)
  • Crucially, compound identification and attribution revealed that fermentation products may be maximally contributing to antimicrobial and antitumor mechanisms rather than intrinsic plant and/or microbial components. (bvsalud.org)
  • Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. (nature.com)
  • The objective was to define the mechanism of the growth inhibition of active hexose correlated compound (AHCC) alone and evaluate its activity in combination with pegylated liposomal doxorubicin (PLD). (researchgate.net)
  • Their current application in oncology has revolutionized cancer treatment by improving the antitumor activity of several chemotherapeutic agents. (mdpi.com)
  • Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. (medsci.org)
  • We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. (nature.com)
  • Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. (nature.com)
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Target based screening is likely to provide very good drug candidates for monogenic diseases, and the following collection of manuscripts is not meant to discourage the use of target based approaches. (docksci.com)
  • Here, target agnostic approaches using phenotypic assays may offer significant benefit. (docksci.com)
  • Viswanathan and colleagues reviewed the recent progress in the culture of hPSCs with emphasis on the importance of the environment surrounding these cells and high content analysis approaches for assay development. (docksci.com)
  • During his six year stay at GNF, Dr. Gray became the director of biological chemistry where he supervised a group of over fifty researchers integrating chemical, biological and pharmacological approaches towards the development of new experimental drugs. (stanford.edu)
  • Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called 'gatekeeper' residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR. (stanford.edu)
  • The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)
  • Updated treatment recommendations for the therapy of rheumatoid arthritis (RA) in South Africa advocate early diagnosis, prompt initiation of disease-modifying anti-rheumatic drugs (DMARDs), and an intense treatment strategy where disease activity is assessed with a composite score such as the Simplified Disease Activity Index (SDAI). (samj.org.za)
  • His achievements in understanding the role of physiochemical properties in drug activity, more precisely in the disposition of medicines ought to be particularly recognised. (efmc.info)
  • Keating's programme aims to elucidate full impurity profiles for drugs in relation to the full synthetic pathway employed. (soci.org)
  • Screening in vivo may be feasible, if a good starting point for Medicinal Chemistry and a clear strategy for differentiation exist. (docksci.com)
  • Library has been assembled using in house structural biology insight, molecular stimulation-modeling, virtual screening of ChemDiv's novel chemistries and medicinal chemistry filtering/ranking of the resulting hits. (chemdiv.com)
  • Of course, clandestine synthesis of ecstasy and other drugs of abuse is widespread. (soci.org)
  • However, several hurdles need to be overcome before widespread implementation of hPSC-based assays. (docksci.com)
  • Moreover, combinatorial strategy dramatically lowered the inhibitory concentration of Taxol to induce a cytotoxic response, suggesting that Curcumin may have potential for use in combination regimens with Taxol. (rgcb.res.in)
  • These data identify novel therapeutic vulnerabilities and may inform future trials of IGF inhibitory drugs. (nature.com)
  • These findings will assist the development of anti-tumour drugs to treat lung cancer. (oncotarget.com)
  • These drugs may deserve to be tested for their efficacy in the control of prostate cancer using in vivo models. (researchgate.net)
  • Increasing amounts of evidence indicate that autophagy is induced by a number of stressors in tumor cells, such as starvation, growth factor deprivation, hypoxia, damage stimulation and therapeutic drugs, and is an important survival mechanism in response to cellular stress ( 9 ). (spandidos-publications.com)
  • RGCB scientists developed a combination treatment synergism of great effectiveness by combining Curcumin and Taxol. (rgcb.res.in)
  • Some drugs (eg, hydralazine , procainamide , isoniazid , anti-tumor necrosis factor [TNF] drugs) cause a reversible lupus-like syndrome. (msdmanuals.com)
  • Etoposide is still considered a potent, well-tolerated combination partner in innumerable hematologic and solid tumor treatment schedules, including those for malignant lymphomas and lung cancer. (wikipedia.org)
  • In oncology, mouse xenograft models, based on a patient's tumor cells, have been used to select between drugs (Wu et al. (docksci.com)
  • In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods. (medsci.org)
  • The combination of AHCC with PLD demonstrated a 64.1% reduction in tumor growth compared to the untreated group (p value = 0.03) and a 31.2% improvement in tumor response with combination regimen compared to PLD alone. (researchgate.net)
  • 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)
  • Therefore, Src has been considered a target molecule for drug development. (oncotarget.com)
  • Microtubule binding drugs are of special interest as they have important roles in the modulation of cellular functions and many of them act as anticancer agents. (rgcb.res.in)
  • The development of platinum-drug resistance in cancer patients, the general toxicity and severe side effects of platinum drugs however required a different approach in the research of anticancer metal complexes [ 2 ]. (hindawi.com)
  • This low survival may result from the metastasis of cancer cells and arising resistance to drugs. (oncotarget.com)
  • Potential molecular mechanism supporting this synergistic effect was assessed with emphasis on determining whether the combination treatment enhanced inhibition of the anti-apoptotic signal transducers Akt and NF-kB leading to increased activation of caspase mediated apoptosis. (rgcb.res.in)
  • The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review. (frontiersin.org)
  • In addition, rhodomycin A rendered gefitinib-resistant lung adenocarcinoma cells more sensitive to gefitinib treatment, implying a synergistic effect of the combination therapy. (oncotarget.com)
  • Fluorescence in situ hybridization assays revealed that Nup96, a Y-complex nucleoporin, enhances FLC positioning at the nuclear periphery. (bvsalud.org)
  • Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. (nature.com)
  • In 2021, Dr. Gray joined Stanford University where he has joined the Stanford Cancer Institute, Chem-H and the Innovative Medicines Accelerator (IMA) to spur the development of prototype drugs. (stanford.edu)
  • Mar Drugs 19: 361, 2021. (cancer.gov)
  • 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)
  • We describe antitumor activities of vitamin E succinate (VES), an anti-oxidant and fenbendazole (FBZ), a commonly used veterinary anthelmintic. (researchgate.net)
  • Professor Maguire underlined the central importance of organic synthesis to the field of chemical biology and the interfaces with drug development and process development. (soci.org)
  • A large number of potential drug targets have been cloned and functionally expressed, and enormous progress has been made in the development, miniaturization and automation of cell based assays on target molecules recombinantly expressed in mammalian cell lines. (docksci.com)
  • Additional screens for MMTV provirus entry sites in tumors revealed several other upregulated genes that are associated with other gene development pathways such as INT2, INT3, and INT4 [4,5,6]. (chemdiv.com)
  • Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome-wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. (cancerindex.org)
  • The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. (frontiersin.org)
  • Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. (frontiersin.org)
  • This approach has delivered many clinical candidates but relatively few new drugs. (docksci.com)
  • A clinical study to evaluate of the combination of AHCC plus PLD in the treatment of ovarian cancer is being pursued. (researchgate.net)
  • Most of these drugs interact relatively weakly with a number of targets, and the complete profile of their molecular interactions is not well-known. (docksci.com)
  • Utilizing single cell genome, methylome, chromatin accessibility, while RNA or protein from the same cell can be used to profile the transcriptome, and proteome, different single cell omics profiles alone or in combination can serve as building blocks to construct a multi-omics profile for the same cell. (frontiersin.org)
  • Immunosuppressive agents encompassed a large number of drugs, mainly represented by anti-tumour necrosis factor (TNF)-α, anti-retroviral therapy (ARV), azathioprine (AZT), methotrexate (MTX), mycophenolate mofetil (MMF), non-steroidal anti-inflammatory drugs (NSAIDs), rituximab and steroids. (ersjournals.com)
  • Otherwise, patients receiving at least one immunosuppressive drug (especially steroids) are more likely to have an indeterminate result [ 1 , 4 , 7 , 8 ]. (ersjournals.com)
  • We made the hypothesis that the proportion of "bad" responders to mitogen among patients with negative QFT could be underestimated, especially during immunosuppressive drug intake. (ersjournals.com)
  • These recommendations provide practical suggestions for the screening and management of TB and other comorbidities, and offer an approach to monitoring of RA patients. (samj.org.za)
  • Promising examples include anti-microbial assays, cell proliferation, platelet aggregation, and insulin release from pancreatic β-cells. (docksci.com)
  • Since the clandestine chemist is unlikely to engage in rigorous purification of their products, most drugs of abuse contain significant impurities. (soci.org)
  • Recently, production of synthetic peptides is achieved commercially by solid-phase peptide synthesis (SPPS) or in combination with solution phase method pioneered by Robert Bruce Merrifield. (rgcb.res.in)
  • Synthetic DMARDs may be used as monotherapy or in combination, and can be co-prescribed with low-dose corticosteroids if necessary. (samj.org.za)
  • One such biological target was RAS, where decades of attempts had failed (until very recently) to yield anti-cancer drugs directly interfering with RAS function. (cancer.gov)
  • These tools were initially used in RAS target validation and subsequently for isolating drug leads, guided by the intracellular antibody interaction with RAS. (cancer.gov)
  • The limited throughput of phenotypic assays compared to most target-based assays necessitates smaller libraries that are optimized with regard to biological and chemical diversity. (docksci.com)
  • In this review we will discuss how combinations and fusions of different -omic workflows on a single cell level can be used to examine cellular phenotypes, immune effector functions, and even dynamic changes, such as metabolomic state of different cells in a sample or even in a defined tissue location. (frontiersin.org)
  • This may be of concern to the user, but Keating is most interested in the opportunities this gives for forensic linkage of recovered drugs to their production site. (soci.org)
  • In 2D culture, all cells can proliferate at a relatively constant rate in a planar space, and can be provided uniform access to nutrients, oxygen or drugs. (medsci.org)
  • Metronidazole (Flagyl) is a drug used to treat infections and has been studied in the treatment of cancer [10,11] as a radiosensitizer drug, especially for hypoxic cells [9]. (who.int)
  • tizer drug, especially for hypoxic cells [ 9 ]. (who.int)
  • The samples were kept at 4 °C until metronidazole does not show any radiosen- the start of the assay. (who.int)
  • Dr. Gray's research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance. (stanford.edu)
  • and ( iii ) the emergence of biologic disease-modifying anti-rheumatic drugs (DMARDs). (samj.org.za)