PEPITEM

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{{Infobox drug

| image = PEPITEM.svg

| image2 = PEPITEM_structure.png

| width = 300

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| CAS_number = 365226-06-8

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| PubChem = 505189302

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| IUPAC_name = L-seryl-L-valyl-L-threonyl-L-α-glutamyl-L-glutaminylglycyl-L-alanyl-L-α-glutamyl-L-leucyl-L-seryl-L-asparaginyl-L-α-glutamyl-L-α-glutamyl-L-Arginine

| C = 61 | H = 101 | N = 19 | O = 28

| SMILES = O=C(N[C@@H](CCC(=O)N)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@H](O)C)CCC(=O)O

| StdInChI = 1S/C61H101N19O28/c1-25(2)20-36(55(102)78-38(24-82)57(104)77-37(21-40(64)85)56(103)73-32(11-16-43(89)90)51(98)72-33(12-17-44(91)92)53(100)75-35(60(107)108)8-7-19-67-61(65)66)76-54(101)31(10-15-42(87)88)70-48(95)27(5)69-41(86)22-68-50(97)30(9-14-39(63)84)71-52(99)34(13-18-45(93)94)74-59(106)47(28(6)83)80-58(105)46(26(3)4)79-49(96)29(62)23-81/h25-38,46-47,81-83H,7-24,62H2,1-6H3,(H2,63,84)(H2,64,85)(H,68,97)(H,69,86)(H,70,95)(H,71,99)(H,72,98)(H,73,103)(H,74,106)(H,75,100)(H,76,101)(H,77,104)(H,78,102)(H,79,96)(H,80,105)(H,87,88)(H,89,90)(H,91,92)(H,93,94)(H,107,108)(H4,65,66,67)/t27-,28+,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,46-,47-/m0/s1

| StdInChIKey = FNMDPJXMBAIAGR-WSBPUMMXSA-N

}}

PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) is an endogenous polypeptide composed of the 14 amino acids 28–41 of the 14.3.3.ζδ protein, which in turn is a 245 amino-acid product of the YWHAZ gene. It has the sequence SVTEQGAELSNEER. PEPITEM has antiinflammatory effects by inhibiting trafficking of T cells into inflamed tissues. Levels of PEPITEM in the body decline with age, diabetes or rheumatoid arthritis, and decreased PEPITEM levels correlates with increases in chronic inflammation and numerous resulting health issues. Administration of synthetic PEPITEM has been suggested as a treatment for various conditions where inflammation plays a role.{{cite journal | vauthors = Chimen M, McGettrick HM, Apta B, Kuravi SJ, Yates CM, Kennedy A, Odedra A, Alassiri M, Harrison M, Martin A, Barone F, Nayar S, Hitchcock JR, Cunningham AF, Raza K, Filer A, Copland DA, Dick AD, Robinson J, Kalia N, Walker LS, Buckley CD, Nash GB, Narendran P, Rainger GE | title = Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease | journal = Nature Medicine | volume = 21 | issue = 5 | pages = 467–475 | date = May 2015 | doi = 10.1038/nm.3842 | pmid = 25894827 | pmc = 4425550 }}{{cite journal | vauthors = Matsubara H, Shimizu Y, Arai M, Yamagata A, Ito S, Imakiire T, Tsunoda M, Kumagai H, Oshima N | title = PEPITEM/Cadherin 15 Axis Inhibits T Lymphocyte Infiltration and Glomerulonephritis in a Mouse Model of Systemic Lupus Erythematosus | journal = Journal of Immunology | volume = 204 | issue = 8 | pages = 2043–2052 | date = April 2020 | doi = 10.4049/jimmunol.1900213 | pmid = 32169847 }}{{cite journal | vauthors = Pezhman L, Hopkin SJ, Begum J, Heising S, Nasteska D, Wahid M, Ed Rainger G, Hodson DJ, Iqbal AJ, Chimen M, McGettrick HM | title = PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation | journal = Clinical and Experimental Immunology | volume = 212 | issue = 1 | pages = 1–10 | date = April 2023 | doi = 10.1093/cei/uxad022 | pmid = 36891817 | pmc = 10081110 }}{{cite journal | vauthors = Alassiri M, Al Sufiani F, Aljohi M, Alanazi A, Alhazmi AS, Alrfaei BM, Alnakhli H, Alshawakir YA, Alharby SM, Almubarak AY, Alasseiri M, Alorf N, Abdullah ML | title = PEPITEM Treatment Ameliorates EAE in Mice by Reducing CNS Inflammation, Leukocyte Infiltration, Demyelination, and Proinflammatory Cytokine Production | journal = International Journal of Molecular Sciences | volume = 24 | issue = 24 | date = December 2023 | page = 17243 | doi = 10.3390/ijms242417243 | doi-access = free | pmid = 38139072 | pmc = 10743148 }}{{cite journal | vauthors = Lewis JW, Frost K, Neag G, Wahid M, Finlay M, Northall EH, Abudu O, Kemble S, Davis ET, Powell E, Palmer C, Lu J, Rainger GE, Iqbal AJ, Chimen M, Mahmood A, Jones SW, Edwards JR, Naylor AJ, McGettrick HM | title = Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss | journal = Cell Reports. Medicine | volume = 5 | issue = 5 | pages = 101574 | date = May 2024 | doi = 10.1016/j.xcrm.2024.101574 | pmid = 38776873 | pmc = 11148860 }}{{cite journal | vauthors = Hopkin SJ, Nathan P, Pezhman L, Begum J, Manning JE, Quinn LM, Rainger GE, McGettrick HM, Iqbal AJ, Chimen M | title = Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention | journal = npj Aging | volume = 10 | issue = 1 | pages = 33 | date = July 2024 | doi = 10.1038/s41514-024-00160-6 | pmid = 39025913 | pmc = 11258258 }}{{cite journal | vauthors = Alassiri M, Al Sufiani F, Aljohi M, Alanazi A, Alhazmi AS, Alrfaei BM, Alnakhli H, Alasseiri M, Alorf N, Abdullah ML | title = Prophylactic administration of PEPITEM in experimental autoimmune encephalomyelitis delays disease onset, inhibits leukocyte infiltration, and alleviates severity | journal = International Journal of Clinical and Experimental Pathology | date = 2024 | volume = 17 | issue = 12 | pages = 492–505 | doi = 10.62347/LTAO2386 | pmid = 39802871 | pmc = 11711485 }}{{cite journal | vauthors = Saviano A, Apta B, Tull S, Pezhman L, Fatima A, Sevim M, Mete A, Chimen M, Schettino A, Marigliano N, McGettrick HM, Iqbal AJ, Maione F, Rainger GE | title = PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis | journal = Pharmacological Research | volume = 213 | pages = 107624 | date = March 2025 | doi = 10.1016/j.phrs.2025.107624 | pmid = 39855372 | doi-access = free }}