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dipeptidyl peptidase 4

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Target id: 1612

Nomenclature: dipeptidyl peptidase 4

Family: S9: Prolyl oligopeptidase

Contents:

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 | bile canaliculus domain-specific membrane glycoprotein | dipeptidyl peptidase IV | DPP IV | GP110 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
Alphafold P27487 (Hs), P28843 (Mm), P14740 (Rn)
BRENDA 3.4.14.5
CATH/Gene3D 3.40.50.1820
ChEMBL Target CHEMBL284 (Hs), CHEMBL3883 (Mm), CHEMBL4653 (Rn)
DrugBank Target P27487 (Hs)
Ensembl Gene ENSG00000197635 (Hs), ENSMUSG00000035000 (Mm), ENSRNOG00000030763 (Rn)
Entrez Gene 1803 (Hs), 13482 (Mm), 25253 (Rn)
Human Protein Atlas ENSG00000197635 (Hs)
KEGG Enzyme 3.4.14.5
KEGG Gene hsa:1803 (Hs), mmu:13482 (Mm), rno:25253 (Rn)
OMIM 102720 (Hs)
Pharos P27487 (Hs)
RefSeq Nucleotide NM_001935 (Hs), NM_001159543 (Mm), NM_010074 (Mm), NM_012789 (Rn)
RefSeq Protein NP_001926 (Hs), NP_034204 (Mm), NP_001153015 (Mm), NP_036921 (Rn)
SynPHARM 78493 (in complex with alogliptin)
81938 (in complex with compound 1 (Xiao et al. 2014))
78503 (in complex with linagliptin)
78507 (in complex with saxagliptin)
78465 (in complex with sitagliptin)
85060 (in complex with teneligliptin)
78481 (in complex with vildagliptin)
UniProtKB P27487 (Hs), P28843 (Mm), P14740 (Rn)
Wikipedia DPP4 (Hs)
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:  12
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 3
⤷ pKi 9.7 (Ki 1.8x10-10 M) [3]
saxagliptin Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 9.2 pKi 7
⤷ pKi 9.2 (Ki 6x10-10 M) [7]
omarigliptin Small molecule or natural product Primary target of this compound Hs Inhibition 9.1 pKi 2
⤷ pKi 9.1 (Ki 8x10-10 M) [2]
linagliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pKi 6
⤷ pKi 9.0 (Ki 1x10-9 M) [6]
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 10
⤷ pKi 8.9 (Ki 1.4x10-9 M) [10]
ZY15557 Small molecule or natural product Primary target of this compound Hs Competitive 8.3 pKi 8
⤷ pKi 8.3 (Ki 5.53x10-9 M) [8]
vildagliptin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pKi 7
⤷ pKi 7.8 (Ki 1.7x10-8 M) [7]
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 14
⤷ pIC50 9.4 (IC50 3.7x10-10 M) [14]
alogliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.5 pIC50 13
⤷ pIC50 8.5 (IC50 3.4x10-9 M) [13]
anagliptin Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 3.8x10-9 M) [9]
Description: Inhibition of human recombinant DPP-4 in vitro
cofrogliptin Small molecule or natural product Approved drug Hs Inhibition 8.4 pIC50 15
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [15]
sitagliptin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [4]
vildagliptin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 1x10-8 M) [1]
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 12
⤷ pIC50 6.6 (IC50 2.328x10-7 M) [12]
compound 9 [PMID: 20718420] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.7 pIC50 11
⤷ pIC50 <4.7 (IC50 >2x10-5 M) [11]
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 5
⤷ pKd ~10.0 (Kd ~1x10-10 M) [5]
Immuno Process Associations
Immuno Process:  Barrier integrity
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  B cell (activation)

References

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1. 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]

2. 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]

3. 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]

4. 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]

5. 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.

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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.

13. 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]

14. 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]

15. Zhang C, Ye F, Wang J, He P, Lei M, Huang L, Huang A, Tang P, Lin H, Liao Y et al.. (2020) Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes. J Med Chem, 63 (13): 7108-7126. [PMID:32452679]

How to cite this page

S9: Prolyl oligopeptidase: dipeptidyl peptidase 4. Last modified on 25/02/2025. Accessed on 25/04/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1612.