产品描述:
TG101348 is a JAK2 inhibitor (IC50 = 3 nM for wild-type and JAK2V617F enzymes).{61888} 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.{61889} 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.{61888}