5-[2,4-二羟基-5-异丙基苯基]-N-乙基-4-[4-(4-吗啉基甲基)苯基]-3-异恶唑甲酰胺

溶解度:Unknown

储存条件:at -20℃ 2 years

生物活性

TG101209, an orally bioavailable small molecule that potently inhibits JAK2 (IC₅₀=6 nM), FLT3 (IC₅₀=25 nM) and RET (IC₅₀=17 nM) kinases, with significantly less activity against other tyrosine kinases including JAK3 (IC₅₀=169 nM). TG101209 inhibited growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC₅₀ of 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations

参考文献

TG101209, a small molecule JAK2-selective kinase inhibitor
potently inhibits myeloproliferative disorder-associated JAK2V617F
and MPLW515L/K mutations. Pardanani A, Hood J, Lasho T, Levine
RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R,