TG101209是一種選擇性的JAK2抑制劑，IC50為6 nM，對Flt3和RET作用效果稍弱，IC50分別為25 nM和17 nM，作用于JAK2比作用于JAK3選擇性高30倍左右，對JAK2V617F和MPLW515L/K突變型敏感。TG101209 is an orally bioavailable, small molecule, ATP-competitive inhibitor towards several tyrosine kinases. TG101209 inhibits growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC50 of B200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209 inducs cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3. TG101209 suppresses growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations. TG101209 significantly reduces STAT5 phosphorylation without affecting the total amount of STAT5 protein. TG101209 inhibits survivin and reduces phosphorylation of STAT3 in HCC2429 and H460 lung cancer cells. TG101209 results in radio sensitization of HCC2429 and H460 lung cancer cells in vitro. A recent study indicates TG101209 abrogates BCR-JAK2 and STAT5 phosphorylation, decreases Bcl-xL expression and triggered apoptosis of transformed Ba/F3 cells.100 mg/kg of TG101209 effectively prolongs the survival in JAK2V617F-induced disease (10 days). Compared with placebo-treated animals, TG101209-treated animals exhibit statistically significant, dose-dependent reduction in the circulating tumor cell burden at day +11 to 20%.TG101209是一種選擇性的JAK2抑制劑，無細胞試驗中IC50為6 nM，對Flt3和RET (c-RET)作用效果稍弱，IC50分別為25 nM和17 nM，作用于JAK2比作用于JAK3選擇性高30倍左右，對JAK2V617F和MPLW515L/K突變型敏感。

Target	Value
JAK2 (Cell-free assay)	6 nM
RET (Cell-free assay)	17 nM
FLT3 (Cell-free assay)	25 nM
JAK3 (Cell-free assay)	169 nM

TG101209是一種口服生物可利用的，小分子，ATP競爭性的幾種酪氨酸激酶抑制劑。TG101209抑制表達JAK2V617F或MPLW515L突變體的Ba/F3細胞生長，IC50為B200 nM。在表達人JAK2V617F的急性髓細胞性白血病細胞系中，TG101209誘導細胞周期阻滯和細胞凋亡，并抑制JAK2V617F，STAT5和STAT3磷酸化作用。TG101209抑制來自負荷JAK2V617F或MPL515突變體的原代祖細胞中造血細胞集落的生長。 TG101209顯著減少STAT5磷酸化，而不影響STAT5蛋白質(zhì)的總量。 在體外HCC2429和H460肺癌細胞中，TG101209抑制存活素，并降低STAT3的磷酸化作用。TG101209導致體外HCC2429和H460肺癌細胞放射致敏。一項最近的研究表明TG101209廢除BCR-JAK2和STAT5磷酸化，減少Bcl-xL表達，并引起轉(zhuǎn)化的Ba/F3細胞凋亡。

100 mg/kg TG101209有效延長JAK2V617F誘發(fā)的患病(10天)動物的存活時間。與安慰劑處理的動物相比，TG101209處理的動物體內(nèi)循環(huán)腫瘤細胞負荷表現(xiàn)出統(tǒng)計學顯著的，劑量依賴性減少，在+11天時減少比例達到20%。