IPI-549

IPI-549 is an inhibitor of PI3Kgamma (IC50s = 16, 3,200, 3,500, and >8,400 nM for PI3Kgamma, PI3Kalpha, PI3Kbeta, and PI3Kdelta, respectively). It is greater than 100-fold selective for PI3Kgamma over a panel of 468 mutant and nonmutant protein and lipid kinases, including Class II PI3K isoforms, and a panel of 80 G protein-coupled receptors, ion channels, and transporters at 10 µM. It inhibits phosphorylation of AKT S473 in SKOV3, 786-0, RAW 264.7, and RAJI cells and inhibits migration of bone marrow-derived macrophages (BMDMs) (IC50 = 85 nM). IPI-549 sensitizes doxorubicin-resistant SW620/Ad300 cells to P-glycoprotein (P-gp) substrates, such as paclitaxel (IC50s = 710 and 6.7 nM for paclitaxel alone and in combination with IPI-549, respectively), and increases the level of intracellular paclitaxel in SW620/Ad300 cells. It also enhances the tumor growth reduction of paclitaxel (Cay-10461) in an SW620/Ad300 mouse xenograft model when administered at a dose of 3 mg/kg in combination with paclitaxel.Formal Name: 2-amino-N-[(1S)-1-[1,2-dihydro-8-[2-(1-methyl-1H-pyrazol-4-yl)ethynyl]-1-oxo-2-phenyl-3-isoquinolinyl]ethyl]-pyrazolo[1,5-a]pyrimidine-3-carboxamide. CAS Number: 1693758-51-8. Molecular Formula: C30H24N8O2. Formula Weight: 528.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 100 mg/mL, Ethanol: 8 mg/mL. lambdamax: 268, 360 nm. SMILES: O=C(C1=C2N(C=CC=N2)N=C1N)N[C@@H](C)C(N3C4=CC=CC=C4)=CC5=CC=CC(C#CC6=CN(C)N=C6)=C5C3=O. InChi Code: InChI=1S/C30H24N8O2/c1-19(34-29(39)26-27(31)35-37-15-7-14-32-28(26)37)24-16-22-9-6-8-21(13-12-20-17-33-36(2)18-20)25(22)30(40)38(24)23-10-4-3-5-11-23/h3-11,14-19H,1-2H3,(H2,31,35)(H,34,39)/t19-/m0/s1. InChi Key: XUMALORDVCFWKV-IBGZPJMESA-N.