BTX-A51

BTX-A51 is a first-in-class, oral small molecule inhibitor that targets casein kinase 1 alpha (CK1α) and cyclin-dependent kinases 7 and 9 (CDK7/9). By inhibiting these kinases, BTX-A51 induces apoptosis in leukemic cells through activation of p53 and suppression of MCL1 expression. The drug also reduces RNA polymerase II phosphorylation, impacting transcriptional regulation. In phase 1 clinical trials for relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), BTX-A51 demonstrated increased p53 expression, reduced MCL1 levels, and some clinical responses—particularly among patients with RUNX1 mutations. Ex vivo studies suggest synergy with azacitidine and venetoclax. The recommended phase 2 dose is 21 mg three days per week for four weeks in a 28-day cycle[6][9].