Sellas to Showcase SLS009 Potent CDK9 Inhibitor Lowering AML Cell IC50 to 20nM
Sellas’s preclinical studies show SLS009 reduced IC50 from 50nM to 20nM in AML cell lines after repeated dosing, increasing caspase-3 activation and suppressing MCL-1 within 6 hours. SLS009 also induced apoptosis in ASXL1- and TP53-mutant AML models, supporting its development in high-risk genetic subtypes.
1. Enhanced Preclinical Potency
Exposure of AML cell lines to ascending concentrations of SLS009 for six hours increased active caspase-3 and decreased MCL-1 expression, and repeated dosing over eight hours (three doses) lowered the IC50 from 50 nM to about 20 nM, demonstrating stronger apoptotic induction.
2. Activity in High-Risk AML Subtypes
SLS009 showed potent apoptotic effects in cell models harboring ASXL1 and TP53 mutations, genetic alterations linked to poor prognosis and resistance, indicating the compound’s potential to address disease subtypes with limited treatment options.
3. AACR Presentation and Development Pathway
Data on tambiciclib’s optimized dosing schedule and mechanistic impact will be presented at AACR on April 21, underscoring plans to advance SLS009 into combination regimens and clinical evaluation for diverse AML genetic backgrounds.