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dipeptidyl peptidase 8

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Target not currently curated in GtoImmuPdb

Target id: 2356

Nomenclature: dipeptidyl peptidase 8

Family: S9: Prolyl oligopeptidase

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 898 15q22.31 DPP8 dipeptidyl peptidase 8
Mouse - 892 9 C Dpp8 dipeptidylpeptidase 8
Rat - - 8q24 Dpp8 dipeptidylpeptidase 8
Previous and Unofficial Names Click here for help
dipeptidyl peptidase IV-related protein-1 | dipeptidyl peptidase VIII | DP8 | DPP VIII | DPRP1 | dipeptidyl-peptidase 8
Database Links Click here for help
Specialist databases
MEROPS S09.018 (Hs)
Other databases
Alphafold Q6V1X1 (Hs), Q80YA7 (Mm)
BRENDA 3.4.14.5
CATH/Gene3D 3.40.50.1820
ChEMBL Target CHEMBL4657 (Hs)
Ensembl Gene ENSG00000074603 (Hs), ENSMUSG00000032393 (Mm), ENSRNOG00000019105 (Rn)
Entrez Gene 54878 (Hs), 74388 (Mm)
Human Protein Atlas ENSG00000074603 (Hs)
KEGG Enzyme 3.4.14.5
KEGG Gene hsa:54878 (Hs), mmu:74388 (Mm)
OMIM 606819 (Hs)
Pharos Q6V1X1 (Hs)
RefSeq Nucleotide NM_017743 (Hs), NM_130434 (Hs), NM_197960 (Hs), NM_197961 (Hs), NM_028906 (Mm)
RefSeq Protein NP_932064 (Hs), NP_932065 (Hs), NP_569118 (Hs), NP_060213 (Hs), NP_083182 (Mm)
UniProtKB Q6V1X1 (Hs), Q80YA7 (Mm)
Wikipedia DPP8 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.14.5
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
inflammatory protein-10 (IP10) Substrate is endogenous in the given species Hs - - 1
stromal cell-derived factor (SDF-1) Substrate is endogenous in the given species Hs - - 1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
talabostat Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.8 pKi 4
⤷ pKi 8.8 (Ki 1.5x10-9 M) [4]
compound 24dd [PMID: 20684603] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pKi 6
⤷ pKi 6.6 (Ki 2.7x10-7 M) [6]
compound 18 [PMID: 15664838] Small molecule or natural product Primary target of this compound Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.4x10-8 M) [5]
1G244 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 10
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [10]
ICeD-2 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 7
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [7]
tominostat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 9
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [9]
teneligliptin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 11
⤷ pIC50 6.6 (IC50 2.6x10-7 M) [11]
compound 42 [PMID: 37721854] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 3
⤷ pIC50 6.2 (IC50 6x10-7 M) [3]
vildagliptin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.7 pIC50 2
⤷ pIC50 5.7 (IC50 2.2x10-6 M) [2]
compound 9 [PMID: 20718420] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.4 pIC50 8
⤷ pIC50 5.4 (IC50 3.7x10-6 M) [8]

References

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1. Ajami K, Pitman MR, Wilson CH, Park J, Menz RI, Starr AE, Cox JH, Abbott CA, Overall CM, Gorrell MD. (2008) Stromal cell-derived factors 1alpha and 1beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett, 582 (5): 819-25. [PMID:18275857]

2. Benramdane S, De Loose J, Beyens O, Van Rymenant Y, Vliegen G, Augustyns K, De Winter H, De Meester I, Van der Veken P. (2022) Vildagliptin-Derived Dipeptidyl Peptidase 9 (DPP9) Inhibitors: Identification of a DPP8/9-Specific Lead. ChemMedChem, 17 (15): e202200097. [PMID:35760756]

3. Benramdane S, De Loose J, Filippi N, Espadinha M, Beyens O, Rymenant YV, Dirkx L, Bozdag M, Feijens PB, Augustyns K et al.. (2023) Highly Selective Inhibitors of Dipeptidyl Peptidase 9 (DPP9) Derived from the Clinically Used DPP4-Inhibitor Vildagliptin. J Med Chem, 66 (18): 12717-12738. [PMID:37721854]

4. Connolly BA, Sanford DG, Chiluwal AK, Healey SE, Peters DE, Dimare MT, Wu W, Liu Y, Maw H, Zhou Y et al.. (2008) Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety. J Med Chem, 51 (19): 6005-13. [PMID:18783201]

5. Jiaang WT, Chen YS, Hsu T, Wu SH, Chien CH, Chang CN, Chang SP, Lee SJ, Chen X. (2005) Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8. Bioorg Med Chem Lett, 15 (3): 687-91. [PMID:15664838]

6. Meng W, Brigance RP, Chao HJ, Fura A, Harrity T, Marcinkeviciene J, O'Connor SP, Tamura JK, Xie D, Zhang Y et al.. (2010) 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, 53 (15): 5620-8. [PMID:20684603]

7. Moore KP, Schwaid AG, Tudor M, Park S, Beshore DC, Converso A, Shipe WD, Anand R, Lan P, Moningka R et al.. (2022) A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells. ACS Chem Biol, 17 (9): 2595-2604. [PMID:36044633]

8. Tsai TY, Yeh TK, Chen X, Hsu T, Jao YC, Huang CH, Song JS, Huang YC, Chien CH, Chiu JH et al.. (2010) Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein. J Med Chem, 53 (18): 6572-83. [PMID:20718420]

9. Van Goethem S, Matheeussen V, Joossens J, Lambeir AM, Chen X, De Meester I, Haemers A, Augustyns K, Van der Veken P. (2011) Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal?. J Med Chem, 54 (16): 5737-46. [PMID:21711053]

10. Wu JJ, Tang HK, Yeh TK, Chen CM, Shy HS, Chu YR, Chien CH, Tsai TY, Huang YC, Huang YL et al.. (2009) Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor. Biochem Pharmacol, 78 (2): 203-10. [PMID:19439267]

11. Yoshida T, Akahoshi F, Sakashita H, Kitajima H, Nakamura M, Sonda S, Takeuchi M, Tanaka Y, Ueda N, Sekiguchi S et al.. (2012) Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg Med Chem, 20 (19): 5705-19. [PMID:22959556]

How to cite this page

S9: Prolyl oligopeptidase: dipeptidyl peptidase 8. Last modified on 10/10/2023. Accessed on 09/12/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2356.