JTE-013

JTE-013 is a sphingosine-1-phosphate receptor 2 (S1P2) and S1P4 antagonist (IC50s = 17 and 237 nM, respectively). It is selective for S1P2 over S1P1 and S1P3 (IC50s = >10 µM for both). JTE-013 (1 and 10 µM) reverses S1P-induced inhibition of human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) migration. It also reverses S1P-induced inhibition of B16 murine melanoma cell migration. In vivo, JTE-013 (30 mg/kg) reduces lung injury, endothelial dysfunction, and pulmonary edema in a rat model of cecal ligation and puncture-induced sepsis. JTE-013 also inhibits sphingolipid delta(4)-desaturase (DES1, IC50 = 16.8 µM), an effect that is not rescued by the S1P2 agonist CYM5520, as well as sphingosine kinase 1 (SK1) and SK2 (IC50s = 25.1 and 4.3 µM, respectively).Formal Name: N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide. CAS Number: 383150-41-2. Molecular Formula: C17H19Cl2N7O. Formula Weight: 408.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, Ethanol: 30 mg/ml, Ethanol:PBS (pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 216, 248, 304 nm. SMILES: O=C(NNc1cc(C(C)C)c2c(C)nn(C)c2n1)Nc1cc(Cl)nc(Cl)c1. InChi Code: InChI=1S/C17H19Cl2N7O/c1-8(2)11-7-14(22-16-15(11)9(3)25-26(16)4)23-24-17(27)20-10-5-12(18)21-13(19)6-10/h5-8H,1-4H3,(H,22,23)(H2,20,21,24,27). InChi Key: RNSLRQNDXRSASX-UHFFFAOYSA-N. License: Cayman and its customers are licensed to make, have made, sell and use the polynucleotides encoding the S1P2 (Sphingosine 1-Phosphate Receptor 2/ aka Edg 5/ aka PH218) receptor, complementary polynucleotides, and polypeptides and all matter claimed in U.S. Patent No. 5,585,476, U.S. Patent No. 5,856,443, and U.S. Patent No. 6,518,414B1. THIS LICENSE DOES NOT EXTEND TO THE MANUFACTURE AND SALE OF ANY DRUG PRODUCT. Notwithstanding any express or implied warranties to the contrary, including but not limited to Uniform Commercial Code § 2-312(3), Cayman expressly disclaims any and all liability for any claims arising out of or relating to the manufacture and sale of drug products using polynucleotides encoding the S1P2 (Sphingosine 1-Phosphate Receptor 2/ aka Edg 5/ aka PH218) receptor, complementary polynucleotides, and polypeptides or any matter claimed in U.S. Patent No. 5,585,476, U.S. Patent No. 5,856,443, and U.S. Patent No. 6,518,414B1..