9OB2
CDK2/CyclinE bound to compound 11 with P-loop in the EE and CC conformations
This is a non-PDB format compatible entry.
Summary for 9OB2
| Entry DOI | 10.2210/pdb9ob2/pdb |
| Related | 9OB3 9OB4 9OB5 9OB6 |
| Descriptor | Cyclin-dependent kinase 2, G1/S-specific cyclin-E1, (1R,3R)-3-(3-{2-[4-(methanesulfonyl)phenyl]acetamido}-1H-pyrazol-5-yl)cyclopentyl (1-methylcyclopropyl)carbamate, ... (4 entities in total) |
| Functional Keywords | cdk/cyclin, cell cycle |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 67926.94 |
| Authors | Baird, J.,Holliday, M.J. (deposition date: 2025-04-22, release date: 2025-04-30, Last modification date: 2026-05-06) |
| Primary citation | Douthwaite, J.L.,Houde, D.J.,Pardo, E.,Moran, M.,Baird, J.,Meyer, S.R.,Mahjour, B.,Zhao, Q.,Larrow, J.F.,Juang, Y.P.,Holliday, M.J.,Han, C.,Kelley, B.,Dunstan, D.,Billings, K.,Mader, M.M.,Taylor, A.M.,Sexton, J.Z.,Boezio, A.A.,Cernak, T. Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors. J.Med.Chem., 69:9142-9162, 2026 Cited by PubMed Abstract: Modern hit-to-lead optimization winnows down vast chemical spaces of virtual compounds into a selection of potent and selective compounds that can be further profiled with assays. Today, miniaturized chemical synthesis can be performed in high-throughput, shifting the bottleneck to compound purification. Direct-to-biology (D2B) approaches seek to overcome this hurdle by omitting the purification step and submitting reaction mixtures directly to bioassays. Here, we explore nanoscale hit-to-lead optimization through the multistep synthesis of a library of Cdk2/CycE inhibitors, utilizing ultrahigh-throughput experimentation (ultraHTE) in 1,536-well plates. Library performance is assessed by D2B in functional biochemical, bioaffinity, and X-ray crystallographic assays. A selection of potent lead Cdk2/CycE inhibitors identified by D2B was submitted to a phenotypic cell painting assay, which showed cell cycle arrest at G, consistent with Cdk2 inhibition. This miniaturized workflow allows the upper tiers of a typical optimization screening cascade to be performed in a single experiment. PubMed: 41954971DOI: 10.1021/acs.jmedchem.5c03614 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.12 Å) |
Structure validation
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