7Z39

Structure of Belumosudil bound to CK2alpha

Summary for 7Z39

• Entry DOI: 10.2210/pdb7z39/pdb
• Descriptor: Casein kinase II subunit alpha, ACETATE ION, 2-[3-[4-(1~{H}-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-~{N}-propan-2-yl-ethanamide, ... (5 entities in total)
• Functional Keywords: kinase selectivity, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 39815.05

Authors

Brear, P.,Hyvonen, M. (deposition date: 2022-03-01, release date: 2022-10-12, Last modification date: 2024-02-07)

Primary citation

Brear, P.,Hyvonen, M.
Crystal structure of the Rho-associated coiled-coil kinase 2 inhibitor belumosudil bound to CK2 alpha.
Acta Crystallogr.,Sect.F, 78:348-353, 2022

PubMed 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.

PubMed: 36189718
DOI: 10.1107/S2053230X22008767

Experimental method

X-RAY DIFFRACTION (1.6 Å)