8TUC
Unphosphorylated CaMKK2 in complex with CC-8977
Summary for 8TUC
| Entry DOI | 10.2210/pdb8tuc/pdb |
| Descriptor | Calcium/calmodulin-dependent protein kinase kinase 2, (4M)-2-cyclopentyl-4-(7-ethoxyquinazolin-4-yl)benzoic acid, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | calcium/calmodulin dependent protein kinase kinase 2, camkk2, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 33998.06 |
| Authors | Bernard, S.M.,Shanmugasundaram, V.,D'Agostino, L. (deposition date: 2023-08-16, release date: 2023-12-13, Last modification date: 2024-10-30) |
| Primary citation | Chen, Y.,Whitefield, B.,Nevius, E.,Hill, M.,DelRosario, J.,Sinitsyna, N.,Shanmugasundaram, V.,Mukherjee, D.,Shi, L.,Mayne, C.G.,Rousseau, A.M.,Bernard, S.M.,Buenviaje, J.,Khambatta, G.,El Samin, M.,Wallace, M.,Nie, Z.,Sivakumar, P.,Hamann, L.G.,McDonnell, D.P.,D'Agostino, L.A. Identification of Small Molecule Inhibitors and Ligand Directed Degraders of Calcium/Calmodulin Dependent Protein Kinase Kinase 1 and 2 (CaMKK1/2). J.Med.Chem., 66:15750-15760, 2023 Cited by PubMed Abstract: CaMKK2 signals through AMPK-dependent and AMPK-independent pathways to trigger cellular outputs including proliferation, differentiation, and migration, resulting in changes to metabolism, bone mass accrual, neuronal function, hematopoiesis, and immunity. CAMKK2 is upregulated in tumors including hepatocellular carcinoma, prostate, breast, and gastric cancer, and genetic deletion in myeloid cells results in increased antitumor immunity in several syngeneic models. Validation of the biological roles of CaMKK2 has relied on genetic deletion or small molecule inhibitors with activity against several biological targets. We sought to generate selective inhibitors and degraders to understand the biological impact of inhibiting catalytic activity and scaffolding and the potential therapeutic benefits of targeting CaMKK2. We report herein selective, ligand-efficient inhibitors and ligand-directed degraders of CaMKK2 that were used to probe immune and tumor intrinsic biology. These molecules provide two distinct strategies for ablating CaMKK2 signaling in vitro and in vivo. PubMed: 38009718DOI: 10.1021/acs.jmedchem.3c01137 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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