9TF4
ERAP1 in complex with (3R,4R)-1-(3-cyano-6-methylpyridin-2-yl)-4-(propan-2-yl)pyrrolidine-3-carboxylic acid
This is a non-PDB format compatible entry.
Summary for 9TF4
| Entry DOI | 10.2210/pdb9tf4/pdb |
| Descriptor | Endoplasmic reticulum aminopeptidase 1, ZINC ION, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | erap1, peptide binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 106458.71 |
| Authors | Rowland, P. (deposition date: 2025-11-26, release date: 2026-07-08, Last modification date: 2026-07-22) |
| Primary citation | Tinworth, C.P.,Wojno-Picon, J.,Adam, M.,Gade, S.,Hancock, A.P.,Hirst, D.J.,Hutchinson, J.P.,Kitchen, S.,Koumantou, D.,Lea, J.,Lehmann, S.,Liddle, J.,Lonsdale, R.,Neu, M.,Nickels, L.,Phillipou, A.,Rowedder, J.E.,Rowland, P.,Schneck, J.L.,Scott-Stevens, P.,Sheehan, H.,Steidel, M.,Tayler, C.L.,Temponeras, I.,Thang, K.,Tough, D.F.,Vitulli, G.,Wall, I.D.,Young, R.J.,Zinn, N.,Peace, S.,Stratikos, E. Discovery of an Orally Available Potent ER Aminopeptidase 1 (ERAP1) Inhibitor That Enhances Antitumor Responses and Limits Inflammatory Autoimmunity In Vivo . J.Med.Chem., 69:15358-15373, 2026 Cited by PubMed Abstract: Endoplasmic reticulum aminopeptidase 1 (ERAP1) regulates immune responses by proteolytically processing peptides presented by major histocompatibility class I molecules (MHC-I). ERAP1 can reduce the immunogenicity of cancer cells by destroying cancer-associated antigenic peptides or contribute to autoimmunity by generating self-antigenic peptides. ERAP1 inhibition has emerged as a tractable approach for cancer immunotherapy and specific classes of autoimmune diseases. We describe the discovery of a potent and selective ERAP1 inhibitor that targets its regulatory allosteric site. The compound has favorable pharmacokinetics, oral bioavailability, can regulate the immunopeptidome of cancer cells, and enhance tumor antigenicity controlling growth. When administered in the murine collagen-induced arthritis model, we observed no exacerbation of autoimmune responses but rather a dose-dependent therapeutic benefit. Our results demonstrate that ERAP1 inhibition is a tractable approach to modulating immune responses, provide mechanistic insight, and are valuable tools for interrogating ERAP1 biology and further drug development. PubMed: 42324823DOI: 10.1021/acs.jmedchem.6c00029 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.63 Å) |
Structure validation
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