23SR
Cryo-EM structure of CDK2 in complex with CRBN/DDB1 and B11
This is a non-PDB format compatible entry.
Summary for 23SR
| Entry DOI | 10.2210/pdb23sr/pdb |
| EMDB information | 69221 |
| Descriptor | Protein cereblon, Oplophorus-luciferin 2-monooxygenase catalytic subunit,Cyclin-dependent kinase 2,GFP-like fluorescent chromoprotein, DNA damage-binding protein 1, ... (4 entities in total) |
| Functional Keywords | cyclin-dependent kinase 2, cereblon, molecular glue, complex, cell cycle |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 229823.46 |
| Authors | |
| Primary citation | Pei, Y.,Lin, W.,Li, X.,Meng, Y.,Yin, Y.,Pan, B.,Zhou, L.,Cao, L.,Cang, Y.,Jiang, Y.,Lu, W.,Meng, Z. Selective CDK2 Degradation via Noncanonical Recruitment. J.Med.Chem., 2026 Cited by PubMed Abstract: Cyclin-dependent kinase 2 (CDK2) represents a critical therapeutic target in tumors resistant to CDK4/6 inhibitors or with amplification. However, selective inhibition of CDK2 remains challenging owing to the high structural homology among CDKs. In this study, we identify and as cereblon (CRBN)-based molecular glue degraders that selectively degrade CDK2. Ternary complex structures reveal a noncanonical recruitment mode centered on CDK2 Glu57, which bypasses the canonical G-loop/β-hairpin and kinase glycine-rich loop interactions and is stabilized by an extended CRBN-CDK2 interface. Mechanistically, these degraders inhibit retinoblastoma (Rb) phosphorylation and induce G1/S-phase arrest, suppressing CDK2-dependent cell proliferation. further exhibits improved pharmacokinetics, measurable oral bioavailability, and target engagement, achieving intratumoral CDK2 degradation following intraperitoneal administration. Collectively, this study provides a structural blueprint for designing selective kinase degraders and establishes B12 as a chemically tractable probe for targeting CDK2-driven malignancies. PubMed: 42334090DOI: 10.1021/acs.jmedchem.6c01264 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.85 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
