dipeptidyl peptidase 4 | S9: Prolyl oligopeptidase | IUPHAR/BPS Guide to PHARMACOLOGY

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dipeptidyl peptidase 4

Target not currently curated in GtoImmuPdb

Target id: 1612

Nomenclature: dipeptidyl peptidase 4

Family: S9: Prolyl oligopeptidase

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 766 2q23-qter DPP4 dipeptidyl peptidase 4
Mouse - 760 2 C2-D Dpp4 dipeptidylpeptidase 4
Rat - 767 3q21 Dpp4 dipeptidylpeptidase 4
Previous and Unofficial Names
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
Specialist databases
MEROPS S09.003 (Hs)
Other databases
BRENDA 3.4.14.5
CATH/Gene3D 3.40.50.1820
ChEMBL Target CHEMBL284 (Hs)
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)
RefSeq Nucleotide NM_001935 (Hs), NM_010074 (Mm), NM_001159543 (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
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:  10
Enzyme Reaction
EC Number: 3.4.14.5
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
glucagon-like peptide 1 Hs - -

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
talabostat Hs Inhibition 9.7 pKi 2
pKi 9.7 (Ki 1.8x10-10 M) [2]
saxagliptin Hs Inhibition 9.2 pKi 6
pKi 9.2 (Ki 6x10-10 M) [6]
omarigliptin Hs Inhibition 9.1 pKi 1
pKi 9.1 (Ki 8x10-10 M) [1]
linagliptin Hs Inhibition 9.0 pKi 5
pKi 9.0 (Ki 1x10-9 M) [5]
compound 24dd [PMID: 20684603] Hs Inhibition 8.9 pKi 8
pKi 8.9 (Ki 1.4x10-9 M) [8]
ZY15557 Hs Competitive 8.3 pKi 7
pKi 8.3 (Ki 5.53x10-9 M) [7]
vildagliptin Hs Inhibition 7.8 pKi 6
pKi 7.8 (Ki 1.7x10-8 M) [6]
teneligliptin Hs Inhibition 9.4 pIC50 12
pIC50 9.4 (IC50 3.7x10-10 M) [12]
alogliptin Hs Inhibition 8.5 pIC50 11
pIC50 8.5 (IC50 3.4x10-9 M) [11]
sitagliptin Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 8.6x10-9 M) [3]
compound 1 [Xiao et al. 2014] Hs Inhibition 6.6 pIC50 10
pIC50 6.6 (IC50 2.328x10-7 M) [10]
compound 9 [PMID: 20718420] Hs Inhibition <4.7 pIC50 9
pIC50 <4.7 (IC50 >2x10-5 M) [9]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Parameter Reference
begelomab Hs Binding ~10.0 pKd 4
pKd ~10.0 (Kd ~1x10-10 M) [4]

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. 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]

9. 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]

10. 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. Chin.Chem. Lett., 25 (5): 673-676.

11. 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]

12. 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 18/04/2018. Accessed on 20/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1612.