11GY
Crystal structure of selective inhibitor 16 bound at the active site of CDK1
This is a non-PDB format compatible entry.
Summary for 11GY
| Entry DOI | 10.2210/pdb11gy/pdb |
| Descriptor | Cyclin-dependent kinase 1, G2/mitotic-specific cyclin-B1, Cyclin-dependent kinases regulatory subunit 2, ... (10 entities in total) |
| Functional Keywords | kinase, cancer, oncology, inhibitor, selectivity, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 79408.56 |
| Authors | Murray, J.M.,Oh, A.,Kiefer, J.R.,Verma, V.A.,Grandner, J.M.,Parr, B.T. (deposition date: 2026-02-23, release date: 2026-07-08) |
| Primary citation | Verma, V.A.,Grandner, J.M.,Parr, B.T.,Zeng, M.,Ashley, M.,Wang, Y.,Beroza, P.,Carione, P.,Johnson, K.M.,Oh, A.J.,Murray, J.M.,Kiefer, J.R.,Moffat, J.G.,Prangley, M.,Merrick, K.,Vartanian, S.,Hafner, M.,Orr, C.J.,Segal, E.,Levy, E.S.,Wang, J.,Xu, Z.,Wang, S.,Liu, G.,Niu, Y.,Li, X.,Zhang, Q.,Ma, Z.,Sun, M.,Wu, Z.,Zhao, W.,Li, Y.,Zhang, L.,Magnuson, S.R.,Samy, K.E. Utilizing Molecular Dynamics and Mechanistic Pharmacokinetic Studies in the Design of Selective CDK2 Inhibitors. J.Med.Chem., 2026 Cited by PubMed Abstract: Targeting HR-positive breast cancer via the inhibition of CDK4 and CDK6 has become the standard of care. However, progression inevitably occurs, and emerging data suggest the implication of CDK2 in this resistance mechanism. As part of our efforts to target this resistance, we embarked on a medicinal chemistry campaign to selectively inhibit CDK2 over the broadly essential CDK1. In order to obtain selectivity against CDK1, we utilized a molecular dynamics approach focused on interaction with a conserved lysine in the active site. Additionally, we uncovered a unique mechanism of clearance driven by both metabolism and efflux in rats and demonstrated that we could counter efflux-driven clearance with high permeability. Our efforts resulted in compound , which was potent against CDK2, exhibited good selectivity vs CDK4 and CDK1, and had pharmacokinetic properties that enabled evaluation in a CDK2 xenograft model of cancer, where it achieved nearly 80% tumor growth inhibition. PubMed: 42328801DOI: 10.1021/acs.jmedchem.5c03803 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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