7m3z | pdb_00007m3z

Structure of TIM-3 in complex with N-(4-(8-chloro-2-mehtyl-5-oxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)methanesulfonamdide (compound 35)

spinqualitylabelsall models 7m3z, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: CA, YQD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3).,Rietz TA, Teuscher KB, Mills JJ, Gogliotti RD, Lepovitz LT, Scaggs WR, Yoshida K, Luong K, Lee T, Fesik SW J Med Chem. 2021 Oct 1. doi: 10.1021/acs.jmedchem.1c01336. PMID:34597046 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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