35WF

Crystal structure of CHK1 in complex with prexasertib

This is a non-PDB format compatible entry.

Summary for 35WF

• Entry DOI: 10.2210/pdb35wf/pdb
• Descriptor: Serine/threonine-protein kinase Chk1, prexasertib, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• Functional Keywords: kinase, inhibitor, cell cycle, dna damage
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 34420.61

Authors

Pinkerton, A.B. (deposition date: 2026-05-20, release date: 2026-08-05)

Primary citation

Meyer, S.T.,Chowdhry, S.,Elsdon, R.J.,Mauger, J.,Truong, Y.P.H.,Hansen, R.,Plum, J.,Steffy, A.,Pferdekamper, A.,Norman, B.,Garcia, S.,Tse, E.,Apuy, J.,Ardeshiri, A.,Kasibhatla, S.,Hassig, C.A.,Pinkerton, A.B.
Discovery of BBI-355, a Potent, Selective, and Orally Available Checkpoint Kinase 1 Inhibitor for the Treatment of Extrachromosomal DNA Oncogene-Amplified Cancers.
J.Med.Chem., 2026

PubMed Abstract: Checkpoint kinase 1 (CHK1), a master regulator of replication stress, has been investigated as a potential therapeutic target for over two decades. More recently, CHK1 has been implicated as a target for the treatment of ecDNA-driven, oncogene-amplified cancers. However, clinical-stage CHK1 inhibitors have historically faced challenges related to dosing schedule, tolerability, and clinical efficacy, although recent studies suggest that biomarker-driven approaches and alternative dosing strategies may address some of these limitations. Structure-guided optimization led to the discovery of BBI-355, a potent, selective, and orally available CHK1 inhibitor. BBI-355 demonstrates strong antitumor activity when dosed orally in mouse xenograft models, achieving regressions both as a single agent and in combination with targeted therapies. BBI-355 also displays favorable ADMET and PK properties and has been advanced to a clinical trial for patients with oncogene amplified cancers.

PubMed: 42457651
DOI: 10.1021/acs.jmedchem.6c00822

Experimental method

X-RAY DIFFRACTION (1.68 Å)