TG101348

TG101348 is a JAK2 inhibitor (IC50 = 3 nM for wild-type and JAK2V617F enzymes). It is 35-, 334-, and 135-fold selective for JAK2 over JAK1, JAK3, and tyrosine kinase 2 (TYK2), respectively. It is also selective for JAK2 over a panel of 34 kinases at 500 nM but does inhibit FMS-related tyrosine kinase 3 (FLT3) and RET (IC50s = 15 and 48 nM, respectively). TG101348 reduces the proliferation of HEL human erythroleukemic cells as well as Ba/F3 murine hematopoioetic cells expressing JAK2V617F (IC50s = 305 and 270 nM, respectively). It inhibits the differentiation of hematopoietic stem cells and myeloid progenitor cells isolated from patients with the myeloproliferative neoplasm (MPN) polycythemia vera when used at a concentration of 300 nM. TG101348 (60 and 120 mg/kg) improves survival and reduces spleen weight in a syngeneic mouse model of polycythemia vera induced by transplantation of Jak2V617F-expressing whole bone marrow.Formal Name: N-(1,1-dimethylethyl)-3-[[5-methyl-2-[[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]amino]-4-pyrimidinyl]amino]-benzenesulfonamide. CAS Number: 936091-26-8. Synonyms: Fedratinib, SAR302503. Molecular Formula: C27H36N6O3S. Formula Weight: 524.7. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 50 mg/ml, Ethanol: 0.5 mg/ml. lambdamax: 275 nm. SMILES: CC(C)(C)NS(C1=CC=CC(NC2=NC(NC3=CC=C(OCCN4CCCC4)C=C3)=NC=C2C)=C1)(=O)=O. InChi Code: InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31). InChi Key: JOOXLOJCABQBSG-UHFFFAOYSA-N.