APG-3526 / Ascentage Pharma - LARVOL DELTA

Targeting activation of intrinsic apoptotic pathway through Mcl-1 inhibition to delay emergence of acquired resistance of lung cancer to osimertinib. (PubMed, Cancer Lett) - "The combination of osimertinib with an Mcl-1 inhibitor (e.g., S63845 or APG3526) synergistically decreased the survival of these resistant cell lines with enhanced induction of apoptosis including augmentation of mitochondrial cytochrome C and Smac release. This combination effectively eliminated senescence-like drug-tolerant persister cells, which had elevated Mcl-1 levels, and abrogated emergence of acquired resistance to osimertinib as demonstrated using both in vitro cell culture and in vivo animal models. Collectively, these results convincingly demonstrate a novel and effective strategy for delaying the emergence of acquired resistance to osimertinib by targeting activation of the intrinsic apoptotic pathway through Mcl-1 inhibition, warranting further clinical validation of this strategy."

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

"Ascentage Pharma presents APG-3526 as a novel and highly potent MCL-1 inhibitor, showing antitumor activity in xenograft mice models." (@Cortellis)

Preclinical • Oncology

[VIRTUAL] Development of APG-3526 as a novel and highly efficacious MCL-1 inhibitor (AACR-II 2020) - "In conclusion, we have developed a novel and highly potent MCL-1 inhibitor, APG-3526, which displays clinically relevant pharmacokinetic properties and elicits potent antiproliferative and antitumor activities via disrupting MCL-1 complex and triggering caspase activation, especially in MCL-1 driven MM models. These results support APG-3526 as a promising MCL-1inhibitor for further clinical development."

IO Biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Breast Cancer • Cervical Cancer • Chronic Lymphocytic Leukemia • Gynecologic Cancers • Leukemia • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • BCL2 • CASP3