CAY10626

A dual PI3Kα/mTOR kinase inhibitor

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of the 3' hydroxyl position of PIs to produce PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3, important second messengers that modulate the activity of downstream targets Akt and mTOR.1 Aberrant PI3K/Akt is associated with many human cancers. CAY10626 is a potent, dual PI3Kα/mTOR inhibitor with IC50 values of 0.9 and 0.6 nM for the two respective kinases.2 In a tumor cell growth inhibition assay, CAY10626 demonstrates IC50 values of <3 and 13 nM for MDA361 (breast) and PC3 (prostate) cancer cell lines, respectively.2 When administered at 25-50 mg/k to MD361 xenograft mice, phosphorylation of the downstream targets of PI3Kα and mTOR (Akt T308, Akt S473, and S6K) was suppressed, and significant tumor regression was observed.2

624.7

≥98%

O=C(NC1=CC=C(C(N(C)CCN(C)C)=O)C=C1)NC2=CC=C(C3=NC(N4CCOCC4)=C(C=CN5CC(F)(F)F)C5=N3)C=C2

C31H35F3N8O3

1202884-94-3

≥ 4 years

DMF: 15 mg/ml DMSO: 15 mg/ml DMSO:PBS (pH 7.2) (1:10): 0.1 mg/ml

1.Rameh, L.E. and Cantley, L.C. The role of phosphoinositide 3-kinase lipid products in cell function. The Journal of Biological Chemisty 274, 8347-8350 (1999).
2.Chen, Z.,Venkatesan, A.M.,Dehnhardt, C.M., et al. Synthesis and SAR of novel 4-morpholinopyrrolopyrimidine derivatives as potent phosphatidylinositol 3-kinase inhibitors. Journal of Medicinal Chemistry 53(8), 3169-3182 (2010).