MCB-613 / Baylor College of Medicine - LARVOL DELTA

Targeting Steroid Receptor Coactivators for the Treatment of Benign Female Reproductive Disorders. (PubMed, Endocr Connect) - "To inhibit SRC activity, natural compounds (e.g., gossypol, bufalin, verrucarin A) and synthetic small molecules (e.g., SI-2, SI-12, MCB-613) have been developed, demonstrating preclinical efficacy across several human diseases...This review summarizes current knowledge of SRC biology in benign gynecologic disorders, outlines their mechanistic roles in disease progression, and highlights opportunities for clinical translation. Targeting SRCs may ultimately represent a novel, non-hormonal, fertility-preserving therapeutic strategy in women's health."

Journal • Endometriosis • Gynecology • Immunology • Polycystic Ovary Syndrome • Solid Tumor • Uterine Leiomyoma • Women's Health • NCOA3

Transcriptional coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress. (PubMed, J Mol Cell Cardiol) - "We provide evidence that MCB-613-10-1 acts as a protectant against oxidative stress-induced mitochondrial damage. Our data reveal that SRC stimulation of the NRF2 transcriptional network promotes resistance to oxidative stress and highlights a mechanistic approach toward addressing pathologic cardiac remodeling."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Myocardial Infarction • HMOX1

[PREPRINT] MCB-613 exploits a collateral sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer through covalent inhibition of KEAP1 (bioRxiv) - “Here, we used a high-throughput phenotypic small molecule screen to identify MCB-613 as a compound that selectively targets EGFR-mutant, EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) cells harboring diverse resistance mechanisms. Subsequent proteomic and functional genomic screens involving MCB-613 identified its target in this context to be KEAP1, revealing that this gene is selectively essential in the setting of EGFR inhibitor resistance. In-depth molecular characterization demonstrated that (1) MCB-613 binds KEAP1 covalently; (2) a single molecule of MCB-613 is capable of bridging two KEAP1 monomers together; and, (3) this modification interferes with the degradation of canonical KEAP1 substrates such as NRF2.”

Preclinical • Preprint • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A steroid receptor coactivator small molecule "stimulator" attenuates post-stroke ischemic brain injury. (PubMed, Front Mol Neurosci) - "We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia...When given within 30 min post middle cerebral artery occlusion and reperfusion, 10-1 induces lasting protection from tissue damage in the ischemic penumbra concomitant with: (1) promotion of reparative microglia; (2) an increase in astrocyte NRF2 and GLT-1 expression; (3) early microglia activation; and (4) attenuation of astrogliosis. Steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Immunology • Inflammation • Ischemic stroke • Myocardial Ischemia • Vascular Neurology

[VIRTUAL] A Steroid Receptor Coactivator Stimulator MCB-613 Attenuates Adverse Remodeling After Myocardial Infarction (ENDO 2021) - "For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021."

Cardiovascular • Fibrosis • Immunology • Inflammation • Myocardial Infarction • ANIB1 • NCOA3

Wound Healing-related Functions of the p160 Steroid Receptor Coactivator Family. (PubMed, Endocrinology) - "This review will provide an overview of wound healing-related functions of SRCs with a special focus on cellular and molecular interactions important for limiting tissue damage after injury. Finally, we review recent findings showing stimulation of SRCs following cardiac injury with the SRC small molecule stimulator MCB-613 can promote cardiac protection and inhibit pathologic remodeling after myocardial infarction."

Journal • Cardiovascular • Immunology • Myocardial Infarction

Wound Healing-related Functions of the p160 Steroid Receptor Coactivator Family. (PubMed, Endocrinology) - "This review will provide an overview of wound healing-related functions of SRCs with a special focus on cellular and molecular interactions important for limiting tissue damage after injury. Finally, we review recent findings showing stimulation of SRCs following cardiac injury with the SRC small molecule stimulator MCB-613 can promote cardiac protection and inhibit pathologic remodeling after myocardial infarction."

Journal • Cardiovascular • Immunology • Myocardial Infarction

Wound healing-related functions of the p160 steroid receptor co-activator family. (PubMed, Endocrinology) - "This review will provide an overview of wound healing-related functions of SRCs with a special focus on cellular and molecular interactions important for limiting tissue damage after injury. Finally, we review recent findings showing stimulation of SRCs following cardiac injury with the SRC small molecule stimulator MCB-613 can promote cardiac protection and inhibit pathologic remodeling after myocardial infarction."

Journal • Cardiovascular • Immunology • Myocardial Infarction