GDC-0339 is a potent, orally bioavailable and well tolerated pan-Pim kinase inhibitor, with K i s of 0.03 nM, 0.1 nM and 0.02 nM for Pim1 , Pim2 and Pim3 , respectively. GDC-0339 is discovered as a potential treatment of multiple myeloma
In Vitro
GDC-0339 is cytostatic, with an IC 50 of 0.1 μM for MM.1S cells. GDC-0339 treatment reveals a constellation of Pim downstream signaling events consistent with inhibition of Pim kinases. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MM.1S cells Concentration: Incubation Time: 3 days Result: Inhibited cell viability. Western Blot AnalysisCell Line: MM.1S cells Concentration: 0.01 μM, 0.03 μM, 0.09 μM,0.27 μM, 0.83 μM, 2.5 μM Incubation Time: 4 hours Result: Induced a constellation of Pim downstream signaling events consistent with inhibition of Pim kinases.
In Vivo
GDC-0339 (1-300 mg/kg; p.o; daily; for 21 days) is efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models. GDC-0339 has a half-life of t1/2=0.9 h. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female C.B-17 SCID mice, RPMI8226 human multiple myeloma xenograft mouse modelDosage: 1mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg, 300 mg/kg Administration: Oral administration; once daily; for 21 days Result: Showed dose-dependent tumor growth inhibition.
Form:Solid
IC50& Target:Ki: 0.03 nM (Pim1), 0.1 nM (Pim2), 0.02 nM (Pim3)
