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WM-1119

CAS No. : 2055397-28-7

MCE 站：WM-1119

产品活性：WM-1119 是强效的、选择性 KAT6A 抑制剂，淋巴瘤细胞中测得对 KAT6A 的 IC₅₀ 值为 0.25 μM，对 KAT6A，KAT5，KAT7 的结合 K_D 值分别为 2 nM，2.2 μM，0.5 μM。

研究领域：Epigenetics

作用靶点：Histone Acetyltransferase

In Vitro: WM-1119 induces cell cycle exit ａnd cellular senescence without causing DNA damage. WM-1119 is 1,100-fold ａnd 250-fold more active against KAT6A than against KAT5 or KAT7, respectively, ａnd so shows greater specificity for KAT6A than does WM-8014. Treatment of MEFs with WM-1119 results in cell cycle arrest in G1 ａnd a senescence phenotype similar to that seen upon treatment with WM-8014. Notably, the activity of WM-1119 in this cell-based assay is an order of magnitude greater than WM-8014 ａnd WM-1119 is able to induce cell cycle arrest at 1 μM. Treatment with WM-1119 inhibits the proliferation of the EMRK1184 lymphoma cells in vitro, WM-1119 (IC₅₀=0.25 μM) is ninefold more active than WM-8014 (IC₅₀=2.3 μM), as expected on the basis of reduced protein binding.

In Vivo: By day 14, the cohorts that are treated four times per day with WM-1119 have arrested tumour growth, with the exception of one mouse that does not respond. Spleen weights in the WM-1119-treatment group (treated four times per day) are substantially lower than spleen weights in the vehicle-treated group. Treatment with WM-1119 three times per day leads to a significant reduction in tumour burden ａnd spleen weight, but is not as effective as treatment four times per day. WM-1119 is well-tolerated; mice show no generalized ill effects ａnd weight loss is not observed. The proportion ａnd overall number of tumour cells is substantially reduced by WM-1119 treatment (four times per day).

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