A5035004504- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- Cancer-related Molecular Pathways
- Chemical Synthesis and Analysis
- Microtubule and mitosis dynamics
- Carbohydrate Chemistry and Synthesis
- Synthetic Organic Chemistry Methods
- Traditional and Medicinal Uses of Annonaceae
- Cyclopropane Reaction Mechanisms
- Advanced Breast Cancer Therapies
- Crystallization and Solubility Studies
- Tryptophan and brain disorders
- Biochemical and Molecular Research
- Pharmacological Receptor Mechanisms and Effects
- X-ray Diffraction in Crystallography
- Mass Spectrometry Techniques and Applications
- Histone Deacetylase Inhibitors Research
- Synthesis and Biological Evaluation
- Chemical Synthesis and Reactions
- Fluorine in Organic Chemistry
- Synthesis and Reactions of Organic Compounds
- Synthesis and Reactivity of Heterocycles
- Epigenetics and DNA Methylation
- Pharmacogenetics and Drug Metabolism
Bristol-Myers Squibb (United States)
2004-2023
Bristol-Myers Squibb (Germany)
2014
Albany Molecular Research (United States)
2008
Hunter College
1994-1995
N-Acyl-2-aminothiazoles with nonaromatic acyl side chains containing a basic amine were found to be potent, selective inhibitors of CDK2/cycE which exhibit antitumor activity in mice. In particular, compound 21 [N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide, BMS-387032], has been identified as an ATP-competitive and CDK2-selective inhibitor selected enter Phase 1 human clinical trials agent. cell-free enzyme assay, showed IC(50) = 48 nM was 10-...
High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable plasma, we have stabilized it to metabolic hydrolysis by replacing the moiety with a 5-ethyl-substituted oxazole 14. Combinatorial parallel synthesis provided rapid analysis structure-activity relationship (SAR) for these inhibitors CDK2, over 100 analogues IC(50) values 1-10 nM range were rapidly prepared....
Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors γ-secretase mediated signaling Notch1/2/3/4 receptors. On the basis its robust vivo efficacy at tolerated doses Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as candidate for clinical evaluation.
This article reports the design, synthesis, and evaluation of a novel class molecules intermediate size (approximately 7000 Da), which possess both targeting effector functions antibodies. These compounds—called synthetic antibody mimics prostate cancer (SyAM-Ps)—bind simultaneously to prostate-specific membrane antigen Fc gamma receptor I, thus eliciting highly selective cell phagocytosis. SyAMs have potential combine advantages small-molecule biologic therapies, may address many drawbacks...
Abstract Despite an excellent initial response to first-line hormonal treatment, most patients with metastatic prostate cancer will succumb a hormone-refractory form of the disease. Because these tumors are still dependent on functional androgen receptor (AR), there is need find novel and more potent antiandrogens. While searching for small molecules that bind AR inhibit its transcriptional activity, BMS-641988 was discovered. This antiandrogen showed increased (>1 log) potency...
BMS-641988 (23) is a novel, nonsteroidal androgen receptor antagonist designed for the treatment of prostate cancer. The compound has high binding affinity AR and acts as functional in vitro. efficacious multiple human cancer xenograft models, including CWR22-BMSLD1 where it displays superior efficacy relative to bicalutamide. Based on its promising preclinical profile, was selected clinical development.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,2-O-Isopropylidenefuranose Templates for the Synthesis of Complex Cyclic Ethers via Neighboring Group Participation by Acetal Ring OxygenWeifang Shan, Phyllis Wilson, Wei Liang, and David R. MootooCite this: J. Org. Chem. 1994, 59, 26, 7986–7993Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December...
Abstract Simple monosaccharides, due to their ready availability and richly functionalized nature, have often proven practical in the preparation of complex natural products.1 Important elements these strategies usually entail stereoselective introduction substituents on carbohydrate template, timely elaboration cyclic acetal, which represents a masked hydroxyaldehyde, into acyclic structures. Regarding stereo-selectivity, several methodologies are available for stereogenic centers at ‘on...
IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety cancers, including metastatic melanoma and renal cell carcinoma. We recently reported identification several novel heme-displacing inhibitors, clinical molecules linrodostat (BMS-986205) BMS-986242. Both contain quinolines that, while being present in successful medicines, are known to be potentially susceptible oxidative metabolism. Efforts swap this quinoline with an alternative aromatic system led...
Abstract For see ChemInform in Full Text.
Abstract Deregulation of the Notch pathway has been shown to be oncogenic in numerous tissue types including T-cell acute lymphoblastic leukemia (T-ALL), breast cancer, non-small cell lung and colorectal carcinoma. signal activation can cause uncontrolled proliferation, restrict differentiation leading increased self-renewal capacity, evasion apoptosis, enhancement angiogenesis metastasis. There is increasing evidence that plays a role maintenance survival cancer stem cells. γ-Secretase...
Supplementary Figure 1 from Discovery of BMS-641988, a Novel and Potent Inhibitor Androgen Receptor Signaling for the Treatment Prostate Cancer