AZD 6482

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of the 3' hydroxyl position of PIs to produce the second messengers PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3. PI3Kalpha, beta, and delta are class 1A enzymes composed of p110 and p85 subunits, whereas PI3Kgamma is a class 1B PI3K composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit. AZD 6482 is a PI3K inhibitor that targets the beta isoform more potently than PI3Kdelta, PI3Kgamma, or PI3Kalpha (IC50s = 0.69, 13.6, 47.8, and 136 nM, respectively). It displays 80-fold selectivity for PI3Kbeta over PI3k-C2 and DNA-PK and more than 1,000-fold over other PI3K-related kinases. AZD 6482 blocks Akt signaling and tumor growth in a large number of cancer cell lines, including those that are dependent on PI3Kbeta activation or PTEN loss. AZD 6482 (20 mg/kg, i.p.) suppresses the growth of PTEN-deficient xenograft tumors in mice. It also produces an anti-thrombotic effect in dogs without an increase in bleeding time or blood loss.Formal Name: 2-[[(1R)-1-[7-methyl-2-(4-morpholinyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]-benzoic acid. CAS Number: 1173900-33-8. Synonyms: KIN-193. Molecular Formula: C22H24N4O4. Formula Weight: 408.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 10 mg/ml, Ethanol: 5 mg/ml. lambdamax: 218, 268, 342 nm. SMILES: O=C1N2C(C([C@@H](C)NC3=C(C(O)=O)C=CC=C3)=CC(C)=C2)=NC(N4CCOCC4)=C1. InChi Code: InChI=1S/C22H24N4O4/c1-14-11-17(15(2)23-18-6-4-3-5-16(18)22(28)29)21-24-19(12-20(27)26(21)13-14)25-7-9-30-10-8-25/h3-6,11-13,15,23H,7-10H2,1-2H3,(H,28,29)/t15-/m1/s1. InChi Key: IRTDIKMSKMREGO-OAHLLOKOSA-N.