AT-13148

AT-13148 is an orally bioavailable and ATP-competitive multi-AGC kinase inhibitor. It inhibits Akt1, 2, and 3 (IC50s = 38, 402, and 50 nM, respectively), in addition to other AGC kinase family members p70S6K, PKA, ROCK1, and ROCK2 (IC50s = 3-8 nM). AT-13148 inhibits growth of cancer cell lines with genetic mutations in PI3K-Akt-mTOR and RAS-RAF signaling pathways (GI50s = 1.54-3.77 µM). In vivo administration of AT-13148 (50 mg/kg, p.o.) inhibits the growth of MES-SA uterine sarcoma and BT474 breast cancer xenografts in mice by inhibiting Akt and p70S6K kinases. AT-13148 also stably inhibits ROCK-dependent phosphorylation of myosin light chain (MLC2) over a 24-hour period in 4599 mouse melanoma cells (EC50 = 0.1 µM). Oral administration at a dose of 40 mg/kg reduces motility of 4699 melanoma cells in murine xenograft model.Formal Name: (alphaS)-alpha-(aminomethyl)-alpha-(4-chlorophenyl)-4-(1H-pyrazol-4-yl)-benzenemethanol. CAS Number: 1056901-62-2. Molecular Formula: C17H16ClN3O. Formula Weight: 313.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml. lambdamax: 257 nm. SMILES: ClC1=CC=C([C@@](CN)(O)C2=CC=C(C3=CNN=C3)C=C2)C=C1. InChi Code: InChI=1S/C17H16ClN3O/c18-16-7-5-15(6-8-16)17(22,11-19)14-3-1-12(2-4-14)13-9-20-21-10-13/h1-10,22H,11,19H2,(H,20,21)/t17-/m0/s1. InChi Key: IIRWNGPLJQXWFJ-KRWDZBQOSA-N.