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Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2022

Synthesis and biological evaluation of Haspin inhibitors: kinase inhibitory potency and cellular activity

Résumé

Haspin (haploid germ cell-specific nuclear protein kinase) offers a potential target for the development of new anticancer drugs. Thus, the identification of new inhibitors targeting this protein kinase is of high interest. However, Haspin inhibitors developed to date show a poor selectivity profile over other protein kinases of the human kinome. Here, we identified a new pyridoquinazoline based inhibitor (4), with excellent inhibitory activity and selectivity for Haspin (IC50 of 50 nM). We describe the structure-activity relationship study including the evaluation of this inhibitor on a large panel of 486 kinases as well as on immortalized or cancer cell lines. In addition, we determined the binding mode of analogue 2a in complex with Haspin using X-ray crystallography.
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hal-03764791 , version 1 (30-08-2022)

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Wael Zeinyeh, Yannick Esvan, Béatrice Josselin, Mathilde Defois, Blandine Baratte, et al.. Synthesis and biological evaluation of Haspin inhibitors: kinase inhibitory potency and cellular activity. European Journal of Medicinal Chemistry, 2022, 236, pp.114369. ⟨10.1016/j.ejmech.2022.114369⟩. ⟨hal-03764791⟩
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