TP-0903

TP-0903 is an inhibitor of the receptor tyrosine kinase Axl (IC50 = 27 nM ). It exhibits greater than 50% inhibition of 11 kinases, including MER, TYRO3, JAK2, ALK, and Abl1, in a panel of 75 kinases at 200 nM, with IC50 values of 3 and 12.4 nM for Aurora A and B, respectively. TP-0903 decreases the phosphorylation of Akt and Axl in GAS6-stimulated, serum-starved PSN-1 pancreatic cancer cells (EC50s = 305 and 222 nM, respectively). It decreases cell viability (IC50 = 6 nM) and induces cell cycle arrest at the G2/M phase in PSN-1 cells when used at a concentration of 30 nM. TP-0903 also reduces the viability of colorectal cancer (CRC) cell lines with IC50 values ranging from 4.5 to 123 nM. It exhibits 69 and 44% tumor growth inhibition in an HCT116 mouse xenograft model and a K-Ras-mutant CRC patient-derived xenograft (PDX) mouse model, respectively, when administered at a dose of 40 mg/kg.Formal Name: 2-[[5-chloro-2-[[4-[(4-methyl-1-piperazinyl)methyl]phenyl]amino]-4-pyrimidinyl]amino]-N,N-dimethyl-benzenesulfonamide. CAS Number: 1341200-45-0. Molecular Formula: C24H30ClN7O2S. Formula Weight: 516.1. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 1 mg/ml (heating/sonication). lambdamax: 281, 330 nm. SMILES: CN1CCN(CC2=CC=C(NC3=NC(NC4=C(S(N(C)C)(=O)=O)C=CC=C4)=C(Cl)C=N3)C=C2)CC1. InChi Code: InChI=1S/C24H30ClN7O2S/c1-30(2)35(33,34)22-7-5-4-6-21(22)28-23-20(25)16-26-24(29-23)27-19-10-8-18(9-11-19)17-32-14-12-31(3)13-15-32/h4-11,16H,12-15,17H2,1-3H3,(H2,26,27,28,29). InChi Key: YUAALFPUEOYPNX-UHFFFAOYSA-N.