Information
Tenalisib (RP6530) is a potent and selective dualPI3Kδ/γinhibitor withIC50values of 24.5 nM and 33.2 nM for PI3Kδ and PI3Kγ, respectively. Its selectivity over α and β isoforms are more than 300-fold and 100-fold, respectively.
Targets
PI3Kδ (Cell-free assay); PI3Kγ (Cell-free assay) 24.5 nM; 33.2 nM
In vitro
RP6530 is a specific dual PI3K δ/γ inhibitor exhibiting several-fold selectivity against the other PI3K isoforms and 245-kinases. RP6530 causes a dose-dependent inhibition (>50% @ 2-7 μM) in growth of immortalized (Raji, TOLEDO, KG-1, JEKO, REC-1) B-cell lymphoma cells. Effect is more pronounced in the DLBCL cell lines, OCI-LY-1 and OCI-LY-10 (>50% inhibition @ 0.1-0.7 μM), and the reduction in viability is accompanied by corresponding inhibition of pAKT with EC50 of 6 & 70 nM respectively. Treatment of patient-derived primary cells with 4 µM RP6530 causes an increase in cell death. Cells in early apotosis (Annexin V+/PI-) are not different between the DMSO blank and RP6530 samples. RP6530 shows potent inhibitory effect on cancer stem cells in ovarian cancer cell lines. Treatment with 1 μM RP6530 results in G2/M arrest in MM-1S and MM-1R lines with very few cells in the SubG0 phase. It also results in a 70−90% inhibition of pAKT in MM-1S and MM-1R cell lines. Potent modulation of inflammatory response by RP6530 contributes to control tumor microenvironment.
In vivo
The predicted T1/2, Cmax, and AUC0-t at 10 mg dose in human are 9.5 h, 14.0 μM, and 342.0 μM respectively. RP6530 has an excellent pharmacokinetic profile with plasma concentrations reaching well above the EC75 at doses as low as 3 mg/kg in rat and dog for 6-12 h. In addition, RP6530 shows >70 and >100% oral bioavailability with a half-life of 2 and 3 h in rat and dog respectively.
Cell Research(from reference)
Cell lines：MM cell lines, namely, MM-1S and MM-1R
Concentrations：1 μM
Incubation Time：72 h
G2227177