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TG101209

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Chemical Structure| 936091-14-4 同义名 : -
CAS号 : 936091-14-4
货号 : A469558
分子式 : C26H35N7O2S
纯度 : 99%+
分子量 : 509.667
MDL号 : MFCD15528085
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(98.1 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 4.6 mg/mL clear

PO 0.5% CMC-Na 52 mg/mL suspension

生物活性
靶点

  • JAK3

    JAK3, IC50:169 nM

  • JAK2

    JAK2, IC50:6 nM

  • c-RET

    RET, IC50:17 nM
描述 Janus kinase 2 (JAK2) is a tyrosine kinase associated with the pathogenesis of myeloproliferative disorders. TG 101209 is a potent, orally bioavailable, small-molecule JAK2 inhibitor with an IC50 value of 6nM. It exhibits 28-fold potency for JAK2 relative to JAK3 in vitro. TG 101209 also shows inhibitory activities against FLT3 and RET with IC50 values of 25 and 17nM, respectively. TG 101209 inhibited the growth of Ba/F3-V617F and Ba/F3-W515L cells with IC50 values of 170 and 220 nM, respectively, but only had minimal effect on CTLL-2 cell growth with an IC50 value of 3400nM. In HEL cells homozygous for the JAK2V617F allele, treatment with TG 101209 at 4.6-38400nM resulted in a concentration-dependent inhibition of cell growth with an IC50 value of 152nM. TG 101209 also potently inhibited the proliferation of CHRF-288-11 cells with an IC50 value of 16nM. HEL cells treated with 600nM TG 101209 showed an increased percentage of Annexin V-positive cells compared to the background level at 24, 48, and 72h. Treatment of HEL cells with 1200nM TG 101209 for 24h increased the percentage of G0/G1 fraction cells compared with the background level. TG 101209 inhibited STAT5 phosphorylation in Ba/F3-V617F cells with an IC50 value of ~300nM. In a mouse model of JAK2V617F-induced hematopoietic disease, oral administration of TG 101209 (100mg/kg, b.i.d) for 10 days significantly prolonged the survival of animals compared with the vehicle-treated group[3].
作用机制 TG 101209 is a potent, selective JAK2 inhibitor. It docked and minimized in the ATP pocket of JAK2. TG 101209 effectively inhibited JAK2V617F and MPLW515L/K tyrosine kinases both in vitro and in vivo[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.81mL

1.96mL

0.98mL

19.62mL

3.92mL

1.96mL
参考文献

[1]Ma AC, Fan A, et al. A novel zebrafish jak2a(V581F) model shared features of human JAK2(V617F) polycythemia vera. Exp Hematol. 2009 Dec;37(12):1379-1386.e4.

[2]Pardanani A, Hood J, et al. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007 Aug;21(8):1658-68.

[3]Pardanani A, Hood J, Lasho T, et al. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007;21(8):1658-1668. doi:10.1038/sj.leu.2404750