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dipeptidyl peptidase 4

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Target not currently curated in GtoImmuPdb

Target id: 1612

Nomenclature: dipeptidyl peptidase 4

Family: S9: Prolyl oligopeptidase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 766 2q24.2 DPP4 dipeptidyl peptidase 4
Mouse 1 760 2 35.85 cM Dpp4 dipeptidylpeptidase 4
Rat 1 767 3q21 Dpp4 dipeptidylpeptidase 4
Previous and Unofficial Names Click here for help
adenosine deaminase complexing protein 2 | dipeptidyl peptidase IV | DPP IV | GP110 glycoprotein | bile canaliculus domain-specific membrane glycoprotein | T-cell activation antigen CD26 | THAM | ADCP2 | dipeptidyl-peptidase 4
Database Links Click here for help
Specialist databases
MEROPS S09.003 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cocrystal structure of dipeptidyl-peptidase 4 with an indole scaffold inhibitor
PDB Id:  4PV7
Ligand:  compound 1 [Xiao et al. 2014]
Resolution:  3.24Å
Species:  Human
References:  11
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
glucagon-like peptide 1 Substrate is endogenous in the given species Hs - -

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 9.7 pKi 2
pKi 9.7 (Ki 1.8x10-10 M) [2]
saxagliptin Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 9.2 pKi 6
pKi 9.2 (Ki 6x10-10 M) [6]
omarigliptin Small molecule or natural product Primary target of this compound Hs Inhibition 9.1 pKi 1
pKi 9.1 (Ki 8x10-10 M) [1]
linagliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pKi 5
pKi 9.0 (Ki 1x10-9 M) [5]
compound 24dd [PMID: 20684603] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pKi 9
pKi 8.9 (Ki 1.4x10-9 M) [9]
ZY15557 Small molecule or natural product Primary target of this compound Hs Competitive 8.3 pKi 7
pKi 8.3 (Ki 5.53x10-9 M) [7]
vildagliptin Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.8 pKi 6
pKi 7.8 (Ki 1.7x10-8 M) [6]
teneligliptin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.4 pIC50 13
pIC50 9.4 (IC50 3.7x10-10 M) [13]
alogliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.5 pIC50 12
pIC50 8.5 (IC50 3.4x10-9 M) [12]
anagliptin Small molecule or natural product Approved drug Hs Inhibition 8.4 pIC50 8
pIC50 8.4 (IC50 3.8x10-9 M) [8]
Description: Inhibition of human recombinant DPP-4 in vitro
sitagliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 8.6x10-9 M) [3]
compound 1 [Xiao et al. 2014] Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.6 pIC50 11
pIC50 6.6 (IC50 2.328x10-7 M) [11]
compound 9 [PMID: 20718420] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.7 pIC50 10
pIC50 <4.7 (IC50 >2x10-5 M) [10]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
begelomab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding ~10.0 pKd 4
pKd ~10.0 (Kd ~1x10-10 M) [4]
Immuno Process Associations
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes
GO:0001618 virus receptor activity IDA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0002709 regulation of T cell mediated immunity ISO
GO:0031295 T cell costimulation IDA
GO:0042110 T cell activation IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0002709 regulation of T cell mediated immunity ISO
GO:0031295 T cell costimulation IDA
GO:0090024 negative regulation of neutrophil chemotaxis IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation IDA
GO:0090024 negative regulation of neutrophil chemotaxis IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation IDA
GO:0042110 T cell activation IDA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002709 regulation of T cell mediated immunity ISO

References

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1. Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y, Krueger D et al.. (2014) Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J Med Chem, 57 (8): 3205-12. [PMID:24660890]

2. 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]

3. Davis JA, Singh S, Sethi S, Roy S, Mittra S, Rayasam G, Bansal V, Sattigeri J, Ray A. (2010) Nature of action of Sitagliptin, the dipeptidyl peptidase-IV inhibitor in diabetic animals. Indian J Pharmacol, 42 (4): 229-33. [PMID:20927248]

4. Di Naro AF. (2014) Anti-CD26 Antibodies and Uses Thereof. Patent number: EP2767549 A1. Assignee: Adienne S.A.. Priority date: 19/02/2013. Publication date: 20/08/2014.

5. Eckhardt M, Langkopf E, Mark M, Tadayyon M, Thomas L, Nar H, Pfrengle W, Guth B, Lotz R, Sieger P et al.. (2007) 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem, 50 (26): 6450-3. [PMID:18052023]

6. Gupta R, Walunj SS, Tokala RK, Parsa KV, Singh SK, Pal M. (2009) Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets, 10 (1): 71-87. [PMID:19149538]

7. Jain MR, Joharapurkar AA, Kshirsagar SG, Patel VJ, Bahekar RH, Patel HV, Jadav PA, Patel PR, Desai RC. (2017) ZY15557, a novel, long acting inhibitor of dipeptidyl peptidase-4, for the treatment of Type 2 diabetes mellitus. Br J Pharmacol, 174 (14): 2346-2357. [PMID:28452143]

8. Kato N, Oka M, Murase T, Yoshida M, Sakairi M, Yamashita S, Yasuda Y, Yoshikawa A, Hayashi Y, Makino M et al.. (2011) Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg Med Chem, 19 (23): 7221-7. [PMID:22019046]

9. 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]

10. 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]

11. Xiao P, Guo R, Huang S, Cui H, Ye S, Zhang Z. (2014) Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold. ChinChem Lett, 25 (5): 673-676.

12. Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z, Xu H et al.. (2012) Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization. Eur J Med Chem, 52: 205-12. [PMID:22475866]

13. 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 4. Last modified on 24/06/2021. Accessed on 26/07/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1612.