CA2 / ConverGene - LARVOL DELTA

Discovery and anti-tumor activity of 4-(benzylamino)-6-(3,5-dimethylisoxazol-4-yl)quinoline-2(1H)-one (CG13250), a potent, selective and orally bioavailable BET bromodomain inhibitor. (PubMed, Bioorg Med Chem Lett) - "Inhibitors of the BET proteins, in particular BRD4, have demonstrated anti-tumour activities and efficacies in clinical trials. Herein, we describe the discovery of potent and selective inhibitors of BRD4, and demonstrate that the lead compound CG13250 is orally bioavailable and efficacious in a mouse xenograft model of leukemia."

Journal • Hematological Malignancies • Leukemia • Oncology • BRD4

CN470 is a BET/CBP/p300 multi-bromodomain inhibitor and has an anti-tumor activity against MLL-rearranged acute lymphoblastic leukemia. (PubMed, Biochem Biophys Res Commun) - "Further, CN470 also showed anti-tumor effects against an MLL-r ALL patient-derived xenograft model. These findings suggest that inhibition of BET/CBP/p300 by the multi-bromodomain inhibitor, CN470, represents a promising therapeutic approach against MLL-r ALL."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BRD4 • MYC

CG223, a novel BET inhibitor, exerts TGF-β1-mediated antifibrotic effects in a murine model of bleomycin-induced pulmonary fibrosis. (PubMed, Pulm Pharmacol Ther) - "Pulmonary fibrosis is a progressive disease with poor prognosis and limited therapeutic options. Subsequent in vitro studies with murine primary lung fibroblasts showed that the mRNA induction of Thbs1, Itgb3, and Acta2 by TGF-β1 can be inhibited by CG223 in a dose-dependent manner. Taken together, CG223-induced BRD4 inhibition suppressed lung fibrogenesis by affecting multiple genes, including those involved in the triggering of the TGF-β1 autocrine/paracrine loop."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ACTA2 • BRD4 • CD61 • TGFB1

A quinazoline-based bromodomain inhibitor, CN210, ameliorates indomethacin-induced ileitis in mice by inhibiting inflammatory cytokine expression. (PubMed, Drug Dev Res) - "CN210 ameliorates indomethacin-induced ileitis by inhibiting the expression of inflammatory cytokines through the attenuation of NF-κB and MAPK pathways. CN210 thus represents a new mode of therapy for non-steroidal anti-inflammatory drug-induced ileitis and inflammatory bowel disease."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • CREBBP • MPO

[VIRTUAL] Application of BET/CBP/p300 multi-bromodomain inhibitors as a novel therapeutic strategy for MLL-rearranged acute lymphoblastic leukemia (AACR-II 2020) - "Moreover, co-immunoprecipitation assay demonstrated that CN470 reduced the binding of BRD4 to acetylated H3 (H3K27), an effect absent with a reference BET inhibitor, OTX-015. Taken together, CN470 may represent an effective strategy against MLL-r ALL cells.As a confirmatory study, we investigated the in vivo effects of CN470 by using SEMLuc/GFP cells in an orthotopic mouse model of MLL-AF4 leukemia. Mice were orally administered with CN470 (10 mg/kg) once daily resulting in a prolonged survival compared to vehicle control group (mean 37 days vs. 28 days; p=0.0246).In conclusion, simultaneous inhibition of BET/CBP/p300 with a multi-bromodomain inhibitor represents a promising novel therapeutic approach against MLL-r ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • MLL • MYC

Development of a first in class inhibitor of BET bromodomains and dopamine receptor 2 (AACR 2017) - "Therefore, our BRD4/DRD2 dual-active compounds may hold promise as a novel class of therapeutics that interferes with both cancer growth and maintenance by simultaneously interfering with MYC and DRD2 pathways. We currently are investigating these dual-active compounds in multiple in vitro and in vivo models and expect to report the outcomes at the AACR Annual Meeting in 2017."

Acute Myelogenous Leukemia • Biosimilar • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Pancreatic Cancer • Small Cell Lung Cancer