Recent developments in Haspin kinase inhibitors: Structure, synthesis and activities

Area of Science:

• Biochemistry and Molecular Biology
• Medicinal Chemistry
• Cell Biology

Background:

• Haspin (Haploprocess-related nuclear spindle kinase) is an atypical serine/threonine protein kinase crucial for mitosis progression.
• Dysregulation of Haspin is implicated in various cellular processes, making it a target for therapeutic intervention.
• Significant advancements in discovering selective Haspin inhibitors have been reported, particularly in recent years.

Purpose of the Study:

• To review and synthesize recent findings on Haspin inhibitors published since 2022.
• To classify novel Haspin inhibitors based on their chemical families.
• To highlight progress in achieving selectivity for Haspin inhibition.

Main Methods:

• Literature review of patented and journal articles published since 2022.
• Analysis of Haspin inhibitors based on rational drug design principles.
• Classification of inhibitors by chemical scaffolds, including indole, indazole, quinoline, isoquinoline, benzothiophene, and purine derivatives.

Main Results:

• Identification of diverse chemical series, such as indole, indazole, quinoline, isoquinoline, benzothiophene, and purine derivatives, exhibiting potent Haspin inhibitory activity.
• Demonstration of good selectivity profiles for these inhibitors when tested against large kinase panels.
• Progress in rational design strategies leveraging Haspin structure knowledge.

Conclusions:

• Recent research has yielded potent and selective Haspin inhibitors across various chemical families.
• Rational design approaches based on Haspin structure are effective in developing novel inhibitors.
• These findings provide a valuable resource for further development of Haspin-targeted therapeutics.