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Crystal structure of the Rho-associated coiled-coil kinase 2 inhibitor belumosudil bound to CK2α

DOI: 10.1107/S2053230X22008767 DOI Help

Authors: Paul Brear (University of Cambridge) , Marko Hyvonen (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 78

State: Published (Approved)
Published: October 2022
Diamond Proposal Number(s): 25402

Open Access Open Access

Abstract: The small molecule belumosudil was initially identified as a selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) and has recently been approved for the treatment of graft-versus-host disease. However, recent studies have shown that many of the phenotypes displayed upon treatment with belumosudil were due to CK2α inhibition. CK2α is in itself a very promising therapeutic target for a range of conditions and has recently been put forward as a potential treatment for COVID-19. Belumosudil presents a promising starting point for the development of future CK2α inhibitors as it provides a safe, potent and orally bioavailable scaffold. Therefore, several of the major hurdles in drug development have already been overcome. Here, the crystal structure of belumosudil bound to the ATP site of CK2α is presented. This crystal structure combined with modelling studies further elucidates how belumosudil could be developed into a selective and potent CK2α or ROCK2 inhibitor.

Journal Keywords: belumosudil; CK2α inhibition; Rho-associated coiled-coil kinase 2; ROCK2 inhibition; kinase inhibitors; selective inhibitors

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I04-Macromolecular Crystallography

Added On: 28/09/2022 11:41

Acta Crystallographica F - 2022 - Brear - Crystal structure of the Rho‐associated coiled‐coil kinase 2 inhibitor.pdf

Discipline Tags:

Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)