ETC-206

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ETC-206 (ETC-1907206) 是一种新型有效的选择性 MNK1/2 抑制剂，IC50 为 64/86 nM，抑制 HeLa 细胞系中的 eIF4E 磷酸化抑制，IC50 为 321 nM。

ETC-206 (ETC-1907206) is a novel potent, selective MNK1/2 inhibitor with IC50 of 64/86 nM, inhibits eIF4E phosphorylation inhibition in HeLa cell line with IC50 of 321 nM; displays excellent kinase selectivity, inhibits only 2 kinases by >65% at 1 uM against a panel of 104 kinases; demonstrates potent anti-proliferative activity against 25 hematological cancer cell lines with submicromolar IC50, especially against GK-5, DOHH2, AHH1 and P3HR-1 cell lines; prevents BC CML LSC self-renewal in vitro, significantly enhances the anti-tumor activity of dasatinib in BC CML mouse xenograft model.Blood Cancer Phase 1 Clinical(In Vitro):Tinodasertib (ETC-206) inhibits eIF4E phosphorylation in HeLa cell line with an IC50 of 321 nM. The anti-proliferative effects of ETC-206 are assessed in vitro, using CellTiter-Glo viability assay against 25 hematological cancer cell lines including the K562 cell line that overexpresses eIF4E (K562 o/e eIF4E). The IC50s are 1.71 μM, 3.36 μM, 3.70 μM, 4.81 μM, 5.13 μM, 5.05 μM, 6.70 μM, 9.76 μM, and 48.8 μM for SU-DHL-6, GK-5, MC 116, P3HR-1, DOHH2, MPC-11, Ramos.2G6.4C10, AHH-1, and K562 o/e eIF4E cells, respectively.(In Vivo):The antitumor effect of ETC-206 is then assessed in a K562 e/o eIF4E mouse xenograft model after oral administration at 25, 50, or 100 mg/kg alone or in combination with a 2.5 mg/kg fixed dose of Dasatinib throughout the study. Dasatinib at 2.5 mg/kg elicits a tumor growth inhibition (TGI) of 88% with one tumor-free animal. In contrast, ETC-206 alone only yields a maximum TGI of 23% at the highest administered dose of 100 mg/kg, which does not impede tumor growth, and is similar to the nontreated animals. ETC-206 with 2.5 mg/kg of Dasatinib not only increases tumor growth inhibition in a dose-dependent manner but, more importantly leads to 2, 5, and 8 out of 8 tumor-free animals at 25, 50, and 100 mg/kg, respectively. The combination of ETC-206 and Dasatinib inhibits tumor growth at all tested doses, and no weight loss is recorded. Both the combination of ETC-206 and Dasatinib and, on the other hand, the dual MNK1/2 and BCR-ABL1 inhibitors prevent tumor growth in the same mouse xenograft model. ETC-206 has moderate terminal elimination half-life (t1/2=1.7 h, and 1.77 h for mouse (1 mg/kg, i.v.), mouse (5 mg/kg, p.o.)).

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ETC206 | ETC 206 | ETC-1907206

MAPK/ERK Signaling

MNK

MNK

Cancer

Blood cancer

1464151-33-4

408.461

C25H20N4O2

>98% (HPLC)

DMSO : ≥ 50 mg/mL 122.41 mM

N#CC1=CC=C(C2=CN=C3C=CC(C4=CC=C(C(N5CCOCC5)=O)C=C4)=CN32)C=C1

4-(6-(4-(morpholine-4-carbonyl)phenyl)imidazo[1,2-a]pyridin-3-yl)benzonitrile

(-20℃)

With Ice Pack

≥ 2 years