A5000114373- Protein Degradation and Inhibitors
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Advanced Breast Cancer Therapies
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Chromatin Remodeling and Cancer
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Congenital heart defects research
- Multiple Myeloma Research and Treatments
- Quinazolinone synthesis and applications
- Cell Adhesion Molecules Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer, Hypoxia, and Metabolism
- Synthesis of Tetrazole Derivatives
- Angiogenesis and VEGF in Cancer
- Renal Diseases and Glomerulopathies
Arvinas (United States)
2017-2024
259 Background: The Androgen Receptor (AR) remains the principal driver of castration-resistant prostate cancer during transition from a localized to metastatic disease. Most patients initially respond inhibitors AR pathway, but response is often relatively short-lived. majority progressing on enzalutamide or abiraterone exhibit genetic alterations in locus, either form amplifications point mutations gene. Given these mechanisms resistance, our goal eliminate protein using PROteolysis...
Abstract Purpose: Estrogen receptor (ER) alpha signaling is a known driver of ER-positive (ER+)/human epidermal growth factor 2 negative (HER2−) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR, or PI3K inhibitors has become central strategy in the treatment ER+ advanced However, suboptimal ER inhibition and resistance resulting from ESR1 mutation dictates that new therapies are needed. Experimental Design: A medicinal chemistry campaign identified...
Spleen tyrosine kinase (Syk) is an attractive drug target in autoimmune, inflammatory, and oncology disease indications. The most advanced Syk inhibitor, R406, 1 (or its prodrug form fostamatinib, 2), has shown efficacy multiple therapeutic indications, but clinical progress been hampered by dose-limiting adverse effects that have attributed, at least part, to the off-target activities of 1. It expected a more selective inhibitor would provide greater window. Herein we report discovery...
Abstract Prostate cancer is the second leading cause of death in men United States. The androgen receptor (AR) plays critical roles both early disease and advanced prostate cancer. Current therapeutic approaches targeting androgen/AR axis are initially effective, but castration resistant (CRPC) inevitably develops. CRPC tightly linked with increased AR activity via gene overexpression, amplification, gain-of-function mutations. To address these mechanisms AR-dependent tumor growth, we have...
While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer death is one of the drug discovery challenges facing biomedical research era precision oncology. Attempts to eradicate cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals been successful clinic, but they are limited by number targets given inability intracellular proteins. More recently,...
Abstract The Androgen Receptor (AR) remains the principal driver of castration-resistant prostate cancer during transition from a localized to metastatic disease. Most patients initially respond inhibitors AR pathway, but response is often short-lived. majority progressing on enzalutamide or abiraterone exhibit genetic alterations in locus, either form amplifications point mutations gene. Given these mechanisms resistance, our goal eliminate protein using PROteolysis TArgeting Chimera...
ABSTRACT. PDGF-B is of central importance in mesangioproliferative diseases. PDGF-D, a new PDGF isoform, like PDGF-B, signals through the ββ-receptor. The present study first determined that PDGF-D mitogenic for rat mesangial cells and not inhibited by antagonist. Low levels mRNA were detected normal glomeruli. After induction nephritis rats anti–Thy 1.1 mAb, glomerular protein expression increased significantly from days 4 to 9 comparison with nonnephritic rats. Peak occurred 2 d later than...
Abstract Prostate cancer is the second leading cause of death in men United States. The androgen receptor (AR) plays critical roles both early disease and advanced prostate cancer. Current therapeutic approaches targeting androgen/AR axis are initially effective, but castration resistant (CRPC) inevitably develops. CRPC linked with increased AR activity via gene overexpression, amplification, gain-of-function mutations. To address these mechanisms AR-dependent tumor growth, we have developed...
381 Background: The Androgen Receptor (AR) remains the principal driver of castration-resistant prostate cancer during transition from a localized to metastatic disease. Most patients initially respond inhibitors AR pathway, but response is often short-lived. majority progressing on enzalutamide or abiraterone exhibit genetic alterations in locus, either form amplifications point mutations gene. Given these mechanisms resistance, our goal eliminate protein using PROteolysis TArgeting Chimera...
<div>AbstractPurpose:<p>Estrogen receptor (ER) alpha signaling is a known driver of ER-positive (ER<sup>+</sup>)/human epidermal growth factor 2 negative (HER2<sup>−</sup>) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR, or PI3K inhibitors has become central strategy in the treatment ER<sup>+</sup> advanced However, suboptimal ER inhibition and resistance resulting from <i>ESR1</i> mutation...
<p>Supplementary Tables S1-S4 and Figures S1-S16</p>
<p>Extended Methods</p>
<div>AbstractPurpose:<p>Estrogen receptor (ER) alpha signaling is a known driver of ER-positive (ER<sup>+</sup>)/human epidermal growth factor 2 negative (HER2<sup>−</sup>) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR, or PI3K inhibitors has become central strategy in the treatment ER<sup>+</sup> advanced However, suboptimal ER inhibition and resistance resulting from <i>ESR1</i> mutation...
<p>Extended Methods</p>
<p>Supplementary Tables S1-S4 and Figures S1-S16</p>
Abstract The Androgen Receptor (AR) remains the principal driver of castration-resistant prostate cancer during transition from a localized to metastatic disease. Most patients initially respond inhibitors AR pathway, but response is often short-lived. majority progressing on enzalutamide or abiraterone exhibit genetic alterations in locus, either form amplifications point mutations gene. Given these mechanisms resistance, our goal eliminate protein using PROteolysis TArgeting Chimera...