A Fast Method to Monitor Tyrosine Kinase Inhibitor Mechanisms

被引：0

作者：

Fernandez, Alejandro ^{[1
,3
]}

Gairi, Margarida ^{[2
]}

Gonzalez, Maria Teresa ^{[2
]}

Pons, Miquel ^{[1
]}

机构：

[1] Univ Barcelona UB, Dept Quim Inorgan & Organ, Biomol NMR Lab, Barcelona 08028, Spain

[2] Ctr Cientif & Tecnol Univ Barcelona CCiTUB, Barcelona 08028, Spain

[3] Univ Barcelona UB, Fac Pharm, PhD Program Biotechnol, Barcelona 08028, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2024年 / 67卷 / 22期

关键词：

SRC; ACTIVATION; SITE; FLEXIBILITY; LESSONS; BINDING; AP24534; DOMAIN;

D O I：

10.1021/acs.jmedchem.4c02042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Methionine residues within the kinase domain of Src serve as unique NMR probes capable of distinguishing between distinct conformational states of full-length Src, including alternative drug-inhibited forms. This approach offers a rapid method to differentiate between various inhibition mechanisms at any stage of drug development, eliminating the need to resolve the structure of Src-drug complexes. Using selectively 13C-methyl-enriched methionine, spectra can be acquired in under an hour, while natural abundance spectra with comparable information are achievable within a few hours.

引用

页码：20571 / 20579

页数：9

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