A5064728048- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Mechanisms of cancer metastasis
- Peptidase Inhibition and Analysis
- Research on Leishmaniasis Studies
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Renin-Angiotensin System Studies
- Virus-based gene therapy research
- Nanoparticle-Based Drug Delivery
Morpho (United States)
2024
Constellation Pharmaceuticals (United States)
2024
Abstract Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability context of mutations. In this study, we describe discovery tulmimetostat, orally available, clinical stage inhibitor, it...
<div>Abstract<p>Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability context of mutations. In this study, we describe discovery tulmimetostat, orally available, clinical stage...
<p>Tulmimetostat mediated cancer cell phenotypic responses are increased in ARID1A LOF contexts.</p>
<p>Synthetic pathway and characterization of tulmimetostat, a long residence time EZH2 inhibitor.</p>
<p>Additional method information to describe technical aspects of the experiments described in this manuscript</p>
<p>Tulmimetostat demonstrates superior level of tumor PRC2 target gene inducon and correlation with efficacy in a bladder cancer xenograft mouse model.</p>
<p>Tulmimetostat demonstrates superior level of tumor PRC2 target gene inducon and correlation with efficacy in a bladder cancer xenograft mouse model.</p>
<p>In cancer patients tulmimetostat plasma exposure levels correlate with PRC2 target gene expression changes in peripheral blood.</p>
<p>Tulmimetostat improves cisplatin responsiveness in chemotherapy-resistant bladder cancer cells.</p>
<p>Synthetic pathway and characterization of tulmimetostat, a long residence time EZH2 inhibitor.</p>
<div>Abstract<p>Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability context of mutations. In this study, we describe discovery tulmimetostat, orally available, clinical stage...
<p>Additional method information to describe technical aspects of the experiments described in this manuscript</p>
<p>In cancer patients tulmimetostat plasma exposure levels correlate with PRC2 target gene expression changes in peripheral blood.</p>