Inavolisib

Inavolisib is an inhibitor of PI3Kalpha (Ki = 0.034 nM). It is selective for PI3Kalpha over PI3Kbeta, PI3Kdelta, and PI3Kgamma (Kis = 99.7, 12.2, and 18.2 nM, respectively) and is 4.4-fold selective in decreasing the phosphorylated levels of proline-rich Akt substrate 40 kDa (PRAS40) in HCC1954 breast cancer cells, which express wild-type PI3K catalytic subunit p110alpha and p110alpha containing a histidine-to-arginine mutation at position 1047 (p110alphaH1047R), over HDQ-P1 breast ductal carcinoma cells, which express only wild-type p110alpha. Inavolisib (111 nM) induces poly(ADP-ribose) polymerase (PARP) cleavage, a marker of apoptosis, in HCC1954 cells. It reduces the levels of phosphorylated Akt, PRAS40, and mutant p110alpha in HCC1954 cells, but not HDQ-P1 cells, when used at concentrations of 111, 333, and 1,000 nM. In vivo, inavolisib (25 or 50 mg/kg per day) decreases tumor volume in an HCC1954 mouse xenograft model.Formal Name: 2S-[[2-[(4S)-4-(difluoromethyl)-2-oxo-3-oxazolidinyl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]-propanamide. CAS Number: 2060571-02-8. Synonyms: GDC-0077, RG-6114. Molecular Formula: C18H19F2N5O4. Formula Weight: 407.4. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble, Ethanol: Soluble, Methanol: Soluble. SMILES: NC([C@H](C)NC1=CC=C(C2=NC(N3[C@@H](COC3=O)C(F)F)=CN2CCO4)C4=C1)=O. InChi Code: InChI=1S/C18H19F2N5O4/c1-9(16(21)26)22-10-2-3-11-13(6-10)28-5-4-24-7-14(23-17(11)24)25-12(15(19)20)8-29-18(25)27/h2-3,6-7,9,12,15,22H,4-5,8H2,1H3,(H2,21,26)/t9-,12-/m0/s1. InChi Key: SGEUNORSOZVTOL-CABZTGNLSA-N.