The PI3Kinases are important downstream effectors of KRAS signaling. In preclinical studies, buparlisib (BKM120), a PI3K inhibitor, when combined with MEK
inhibitor (PD1056309) led to significant synergistic activity in KRAS mutant
NSCLC cell lines.
PI3K-IN-22 is a PI3Kα/mTOR dual kinase inhibitor. PI3K-IN-22 has IC50s of 0.9, 0.6 nM for PI3Kα and mTOR, respectively. PI3K-IN-22 can be used for the research of cancer[1].
ChEBI: CAY10626 is a member of ureas.
PI3K-IN-22 (25 mg/kg; i.v.) suppresses phosphorylation of Akt T308, Akt S473 and S6K in MDA361 breast tumor cells up to 8 h in MDA361 tumor bearing nude mice demonstrated by biomarker studies[1].
PI3K-IN-22 (50, 25, 10 mg/kg; i.v.; once daily for 5 days weekly; 2 rounds) shows good antitumor efficacy in MDA361 tumor xenograft nude mice model[1].
PI3K-IN-22 (25 mg/kg; i.v.; a single dose) has a blood concentrationsat value of 1731 ng/mL at 8 h[1].
| Animal Model: | MDA361 tumor xenograft nude mice model[1] |
| Dosage: | 50, 25, 10 mg/kg |
| Administration: | i.v., once daily for 5 days weekly (2 rounds) |
| Result: | Exhibited significant tumor regression in 50 mg/kg and no tumor regrowth until day 32.
Exhibited tumor growth inhibition in 25 and 10 mg/kg. |
PI3Kα: 0.9 nM (IC50); mTOR: 0.6 nM (IC50)
[1] Chen Z, et al. Synthesis and SAR of novel 4-morpholinopyrrolopyrimidine derivatives as potent phosphatidylinositol 3-kinase inhibitors. J Med Chem. 2010 Apr 22;53(8):3169-82. DOI:
10.1021/jm901783v
