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表观遗传修饰,如DNA甲基化,在遗传信息的表达中发挥着重要作用。DNA甲基转移酶维持DNA甲基化,是肿瘤化疗的一个有吸引力的靶点

2023-07-06
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Epigenetic modification, like DNA methylation, plays a major role in the expression of genetic information. The DNA methyltransferases (DNMTs), maintain DNA methylation, is an attractive target for tumor chemotherapy. WK-23 displays a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. The PK profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. In vivo pharmacokinetic properties of WK-22, WK-23, WK-27, and DC_517 were performed by Medicilon.

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Reference:

Ennian Li, et al. Design, synthesis, and biological evalsuation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties. J Enzyme Inhib Med Chem. 2022 Dec;37(1):1537-1555. doi: 10.1080/14756366.2022.2079640.

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