Details of Drug-Metabolizing Enzyme (DME)
General Information of Drug-Metabolizing Enzyme (DME) (ID: DEKZQY6)
DME Name | Dipeptidyl peptidase IV (DPP4) | ||||
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Synonyms |
Dipeptidyl peptidase 4; Adenosine deaminase complexing protein 2; Dipeptidyl peptidase 4 membrane form; Dipeptidyl peptidase 4 soluble form; Dipeptidyl peptidase IV membrane form; Dipeptidyl peptidase IV soluble form; T-cell activation antigen CD26; TP103; ADABP; ADCP-2; ADCP2; CD26; DPP IV; DPP4
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Gene Name | DPP4 | ||||
UniProt ID | |||||
INTEDE ID | |||||
3D Structure | |||||
Gene ID | |||||
EC Number | EC: 3.4.14.5 | ||||
Lineage | Species: Homo sapiens | ||||
Sequence |
MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP |
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Function |
This enzyme is involved in the pericellular proteolysis of the extracellular matrix (ECM) in association with FAP, the migration and invasion of endothelial cells into the ECM. It also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. It removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.
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KEGG Pathway | |||||
Reactome Pathway | |||||
Molecular Interaction Atlas (MIA) of This DME
Molecular Interaction Atlas (MIA) | ||||||||||||||||||||||||||||||||||||||||
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3 Approved Drug(s) Metabolized by This DME
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Molecular Expression Atlas (MEA) of This DME
The Drug Therapeutic Target (DTT) Role of This DME
DME DTT Name | Dipeptidyl peptidase 4 (DPP-4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DME DTT Type | Successful | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
7 Approved Drug(s) Targeting This DTT
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20 Clinical Trial Drug(s) Targeting This DTT
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54 Patented Agent(s) Targeting This DTT
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10 Discontinued Drug(s) Targeting This DTT
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4 Preclinical Drug(s) Targeting This DTT
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47 Investigative Drug(s) Targeting This DTT
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References
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17 | Clinical pipeline report, company report or official report of Activx. | ||||
18 | Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes. 2002 Apr;51(4):943-50. | ||||
19 | Efficacy and safety of the dipeptidyl peptidase-4 inhibitor PF-734200 added to metformin in Type 2 diabetes.Diabet Med.2011 Apr;28(4):464-9. | ||||
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22 | DA-1229, a novel and potent DPP4 inhibitor, improves insulin resistance and delays the onset of diabetes. Life Sci. 2012 Jan 2;90(1-2):21-9. | ||||
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34 | In silico fragment-based discovery of DPP-IV S1 pocket binders. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1405-9. | ||||
35 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | ||||
36 | 1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett. 2007 Jun 1;17(11):2966-70. | ||||
37 | Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2362-7. | ||||
38 | Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. | ||||
39 | New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4770-3. | ||||
40 | Development of potent and selective dipeptidyl peptidase II inhibitors. Bioorg Med Chem Lett. 2002 Oct 21;12(20):2825-8. | ||||
41 | Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group. Bioorg Med Chem. 2008 Feb 15;16(4):1613-31. | ||||
42 | [(S)-gamma-(4-Aryl-1-piperazinyl)-l-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors. Bioorg Med Chem Lett. 2007 May 1;17(9):2618-21. | ||||
43 | Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibito... Bioorg Med Chem Lett. 2007 Apr 1;17(7):2005-12. | ||||
44 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
45 | Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett. 2006 Jan 1;16(1):123-8. | ||||
46 | 2-[3-[2-[(2S)-2-Cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]- 1,2,3,4-tetrahydroisoquinoline: a potent, selective, and orally bioava... J Med Chem. 2006 Jan 12;49(1):373-80. | ||||
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48 | Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. | ||||
49 | E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-o ne tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.Eur J Pharmacol.2006 Oct 24;548(1-3):181-7. | ||||
50 | Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999011 delays the occurrence of diabetes in male zucker diabetic fatty rats. Diabetes. 2002 May;51(5):1461-9. | ||||
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53 | Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selective dipeptidyl peptidase-4 (DPP4) inhibitors. J Med Chem. 2010 Aug 12;53(15):5620-8. | ||||
54 | In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805. | ||||
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