7M3Y
Structure of TIM-3 in complex with 8-chloro-2-methyl-9-(3-mehtylpyridin-4-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (compound 22)
Summary for 7M3Y
| Entry DOI | 10.2210/pdb7m3y/pdb |
| Descriptor | Hepatitis A virus cellular receptor 2, (4R,10aP)-8-chloro-2-methyl-9-(3-methylpyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | igv, immune system |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 12663.83 |
| Authors | Rietz, T.A. (deposition date: 2021-03-19, release date: 2021-10-13, Last modification date: 2024-11-13) |
| Primary citation | Rietz, T.A.,Teuscher, K.B.,Mills, J.J.,Gogliotti, R.D.,Lepovitz, L.T.,Scaggs, W.R.,Yoshida, K.,Luong, K.,Lee, T.,Fesik, S.W. Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3). J.Med.Chem., 64:14757-14772, 2021 Cited by PubMed Abstract: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3; HAVCR2) has emerged as an attractive immune checkpoint target for cancer immunotherapy. TIM-3 is a negative regulator of the systemic immune response to cancer and is expressed on several dysfunctional, or exhausted, immune cell subsets. Upregulation of TIM-3 is associated with tumor progression, poor survival rates, and acquired resistance to antibody-based immunotherapies in the clinic. Despite the potential advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has lagged behind that of antibody therapeutics. Here, we describe the discovery of high-affinity small-molecule ligands for TIM-3 through an NMR-based fragment screen and structure-based lead optimization. These compounds represent useful tools to further study the biology of TIM-3 immune modulation in cancer and serve as a potentially useful starting point toward the discovery of TIM-3-targeted therapeutics. PubMed: 34597046DOI: 10.1021/acs.jmedchem.1c01336 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.69 Å) |
Structure validation
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