8alx | pdb_00008alx

Structure of human PD-L1 in complex with inhibitor

spinqualitylabelsall models 8alx, resolution 1.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8alx is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.1Å Ligands: 9KK, ACT, CCS, DAB, DPP, GOL, HYP, MAA, NH2, V6W Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PD1L1_HUMAN Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production. Publication Abstract from PubMed Recent advances in immuno-oncology have opened up new and impressive treatment options for cancer. Notwithstanding, overcoming the limitations of the current FDA-approved therapies with monoclonal antibodies (mAbs) that block the PD-1/PD-L1 pathway continues to lead to the testing of multiple approaches and optimizations. Recently, a series of macrocyclic peptides have been developed that exhibit binding strengths to PD-L1 ranging from sub-micromolar to micromolar. In this study, we present the most potent non-antibody-based PD-1/PD-L1 interaction inhibitor reported to date. The structural and biological characterization of this macrocyclic PD-L1 targeting peptide provides the rationale for inhibition of both PD-1/PD-L1 and CD80/PD-L1 complexes. The IC(50) and EC(50) values obtained in PD-L1 binding assays indicate that the pAC65 peptide has potency equivalent to the current FDA-approved mAbs and may have similar activity to the BMS986189 peptide, which entered the clinical trial and has favorable safety and pharmacokinetic data. The data presented here delineate the generation of similar peptides with improved biological activities and applications not only in the field of cancer immunotherapy but also in other disorders related to the immune system. Structural and biological characterization of pAC65, a macrocyclic peptide that blocks PD-L1 with equivalent potency to the FDA-approved antibodies.,Rodriguez I, Kocik-Krol J, Skalniak L, Musielak B, Wisniewska A, Ciesiolkiewicz A, Berlicki L, Plewka J, Grudnik P, Stec M, Siedlar M, Holak TA, Magiera-Mularz K Mol Cancer. 2023 Sep 7;22(1):150. doi: 10.1186/s12943-023-01853-4. PMID:37679783 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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