Tenalisib

1639417-53-0

C23H18FN5O2

DMSO : >= 100 mg/mL (240.72 mM)

PI3K/Akt/mTOR

Tenalisib (RP6530) is a novel, potent, and selective PI3Kdelta and PI3Kgamma inhibitor with IC₅₀ values of 25 and 33 nM, respectively. IC50 & Target: IC50: 25 nM (PI3Kdelta), 33 nM (PI3Kgamma)^[1] In Vitro: Tenalisib shows selectivity over PI3K alpha (>300-fold) and beta (>100-fold) isoforms. Tenalisib exhibits modest proliferation inhibition (33-46% inhibition 10 uM) in both HEL-RS and HEL-RR cells. Addition of 10 uM tenalisib to ruxolitinib is synergistic resulting in a near-complete inhibition of proliferation (>90% for HEL-RS and >70% for HEL-RR). Addition of 5 uM tenalisib, 4 h prior to the addition of ruxolitinib results in a significant reduction in EC₅₀of ruxolitinib (5.8 uM) in HEL-RR cells. Incubation of 10 uM tenalisib with ruxolitinib for 72 h increases the percent of apoptotic cells (55% in HEL-RS and 37% in HEL-RR) compared to either agent alone (16-27% in HEL-RS and 17-21% in HEL-RR)^[1]. In Vivo: Tenalisib has been well tolerated in subjects with heavily pre-treated relapsed/refractory hematologic malignancies. Reported toxicities are manageable with no DLTs. Single agent activity is evident in difficult-to-treat subjects at >= 200 mg BID^[2].