ABC294640

ABC294640 is an inhibitor of sphingosine kinase 2 (SPHK2, Ki = 9.8 µM). It inhibits SPHK2 (IC50 = 60 µM) without affecting SPHK1 activity up to 100 µM but does reduce SPHK1 isoform a (SPHK1a) protein levels in androgen-independent LNCaP (LNCaP-AI) cells via an SPHK1-indirect, proteasomal-dependent mechanism when used at concentrations ranging from 5 to 25 µM. ABC294640 is inactive against a panel of 20 lipid-regulated kinases at 50 µM. It decreases sphingosine-1-phosphate (S1P) production in MDA-MB-231 cells in a concentration-dependent manner. ABC294640 inhibits proliferation of a variety of cancer cells, including HepG2 liver, A-498 kidney, PANC-1 pancreas, and HT-29 colon cells (IC50s = 6, 12.2, 32.8, and 48.1 µM, respectively). It reduces actin filament polymerization in, and cell migration of, A-498 cells in a scratch assay. Oral administration of ABC294640 (35 and 100 mg/kg every other day) reduces tumor growth in a mouse syngeneic model of mammary adenocarcinoma. It also reduces colonic inflammation in mouse and rat models of Crohn's disease induced by trinitrobenzene sulfonic acid (TNBS).Formal Name: 3-(4-chlorophenyl)-N-(4-pyridinylmethyl)-tricyclo[3.3.1.13,7]decane-1-carboxamide. CAS Number: 915385-81-8. Molecular Formula: C23H25ClN2O. Formula Weight: 380.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 16 mg/ml, DMF:PBS(pH7.2) (1:2): 0.3 mg/ml, DMSO: 0.16 mg/ml. lambdamax: 222, 258 nm. SMILES: O=C(NCC1=CC=NC=C1)[C@]23C[C@](C[C@H](C4)C3)(C5=CC=C(Cl)C=C5)C[C@@H]4C2. InChi Code: InChI=1S/C23H25ClN2O/c24-20-3-1-19(2-4-20)22-10-17-9-18(11-22)13-23(12-17,15-22)21(27)26-14-16-5-7-25-8-6-16/h1-8,17-18H,9-15H2,(H,26,27)/t17-,18+,22+,23-. InChi Key: CAOTVXGYTWCKQE-BRNYJPRKSA-N.