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The discovery of a cyanoquinoline-based series of HIPK4 inhibitors with nanomolar potency is reported, establishing cyanoquinoline ligands as a new chemotype for probing HIPK4 biology and advancing male contraceptive discovery.
A rational design strategy utilizing macrocyclization of a bosutinib-based scaffold provides a foundational framework for the validating HIPK4 as a therapeutic target and a high-quality resource to elucidate its roles in normal physiology and disease.
Homeodomain-interacting protein kinase 4 (HIPK4) remains an understudied member of the dark kinome. While genetic knockout studies suggest its involvement in spermiogenesis and cutaneous squamous cell carcinoma, whether these cellular functions can be recapitulated by pharmacological inhibition remains to be determin...
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