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Newly discovered inhibitor for the treatment of B-cell lymphoma

 Last Update: 2021-11-14
 Source: Internet
 Author: User

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Image: Evaluation of the anti-tumor efficacy of IHMT-EZH2-115 in a xenograft mouse model

Recently, researchers led by Professor Liu Qingsong, Hefei Institute of Material Science, Chinese Academy of Sciences, discovered an effective selective zeste homolog 2 (EZH2) enhancer inhibitor ihht-EZH2-115 for the treatment of b-cell lymphoma
.

EZH2 is the enzyme subunit of polycomb inhibition complex 2
.

As a therapeutic target for the treatment of cancer, it has been extensively studied

In this study, the researchers started with EPZ6438, which showed anti-b-cell lymphoma effects in preclinical models.
Under the guidance of computer-aided drug design, the researchers used focused medicinal chemistry methods to obtain IHMT-EZH2-115
.

Biochemical analysis showed that IHMT-EZH2-115 had a strong inhibitory effect on EZH2 wild type and mutant type
.

At the same time, it shows high selectivity for a wide range of histone methyltransferases

In vivo, IHMT-EZH2-115 showed good oral pharmacokinetic characteristics in two mouse models of diffuse large b-cell lymphoma with EZH2 mutations, Pfeiffer (EZH2 A677G) and karpas422 (EZH2 Y641N), and showed Dose-dependent anti-tumor effect

These results indicate that IHMT-EZH2-115 may be a potential candidate gene for clinical development of EZH2 mutation-driven tumors

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