Target General Infomation
Target ID
T31391
Former ID
TTDS00093
Target Name
Dipeptidyl peptidase IV
Gene Name
DPP4
Synonyms
ADABP; ADCP2; Adenosine deaminase complexing protein 2; Adenosine deaminase complexing protein-2; CD26; DPP 4; DPP IV; DPP-IV; Dipeptidyl peptidase 4; Dipeptidyl peptidase 4 soluble form; Dipeptidyl peptidase IV; T-cell activation antigen CD26; TP103; Tcell activation antigen CD26; DPP4
Target Type
Successful
Disease Autoimmune diabetes [ICD10: E08-E13]
Autism [ICD9: 299; ICD10: F84.0]
Bone marrow transplantation [ICD9: 279.5, 996; ICD10: D89.8, T86]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Hypoglycemia [ICD9: 250.8, 251.0, 251.1, 251.2, 270.3, 775.6, 962.3; ICD10: E16.0-E16.2]
Metabolic disorders [ICD9: 270-279; ICD10: E70-E89]
Non-insulin dependent diabetes [ICD10: E11.9]
Psoriasis [ICD9: 696; ICD10: L40]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Unspecified [ICD code not available]
Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF- kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotionof lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also 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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.
BioChemical Class
Peptidase
Target Validation
T31391
UniProt ID
EC Number
EC 3.4.14.5
Sequence
MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY
VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL
PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF
YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL
CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS
EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN
EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY
TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY
PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT
FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE
YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS
KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP
Drugs and Mode of Action
Drug(s) Alogliptin Drug Info Approved Type 2 diabetes [1], [2]
Anagliptin Drug Info Approved Type 2 diabetes [3], [4]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride Drug Info Approved Type 2 diabetes [5]
Kombiglyze XR/Komboglyze FDC Drug Info Approved Diabetes [6]
Linagliptin Drug Info Approved Type 2 diabetes [7], [8]
Saxagliptin Drug Info Approved Type 2 diabetes [9], [10]
Sitagliptin Drug Info Approved Type 2 diabetes [11], [12], [13]
Vildagliptin Drug Info Approved Type 2 diabetes [14], [15]
Dutogliptin Drug Info Phase 3 Type 2 diabetes [16]
Gemigliptin Drug Info Phase 3 Diabetes [17]
IDDBCP161883 Drug Info Phase 3 Type 2 diabetes [18]
LC-150444 Drug Info Phase 3 Type 2 diabetes [19]
MK-3102 Drug Info Phase 3 Type 2 diabetes [20], [21]
SAND-26 Drug Info Phase 3 Autoimmune diabetes [22], [23]
SaxaDapa FDC Drug Info Phase 3 Diabetes [24], [25]
SYR-472 Drug Info Phase 3 Metabolic disorders [26]
Denagliptin Drug Info Phase 2/3 Type 2 diabetes [27]
IP10 C8 Drug Info Phase 2 Psoriasis [28]
IP10.C8-1 Drug Info Phase 2 Psoriasis [28]
KRP-104 Drug Info Phase 2 Type 2 diabetes [29]
Melogliptin Drug Info Phase 2 Type 2 diabetes [30]
P32/98 Drug Info Phase 2 Autism [31]
PF-00734200 Drug Info Phase 2 Type 2 diabetes [32], [33]
YSCMA Drug Info Phase 1/2 Hematological malignancies [34]
ARI-2243 Drug Info Phase 1 Type 2 diabetes [35]
DA-1229 Drug Info Phase 1 Type 2 diabetes [36]
Teneligliptin Drug Info Phase 1 Type 2 diabetes [37]
ASP8497 Drug Info Preclinical Type 2 diabetes [38]
ER-319711-15 Drug Info Preclinical Type 2 diabetes [39]
LY-2463665 Drug Info Preclinical Type 2 diabetes [40]
ALS 2-0426 Drug Info Discontinued in Phase 2 Type 2 diabetes [41]
Isoleucine thiazolidide DPP IV Drug Info Discontinued in Phase 2 Type 2 diabetes [42]
NVP-DPP728 Drug Info Discontinued in Phase 2 Type 2 diabetes [43]
PSN-9301 Drug Info Discontinued in Phase 2 Diabetes [44]
R-1438 Drug Info Discontinued in Phase 2 Type 2 diabetes [45]
TA-6666 Drug Info Discontinued in Phase 2 Type 2 diabetes [46]
ABT-279 Drug Info Discontinued in Phase 1 Type 2 diabetes [47]
SSR-162369 Drug Info Discontinued in Phase 1 Type 2 diabetes [48]
TAK-100 Drug Info Discontinued in Phase 1 Diabetes [49]
DSP-7238 Drug Info Terminated Diabetes [50]
PT-630 Drug Info Terminated Type 2 diabetes [51]
Inhibitor (+/-)-6-(2-chlorophenyl)cyclohex-3-enamine Drug Info [52]
(1-phenylcyclopentyl)methanamine Drug Info [53]
(1R,2R)-1,2-diphenylethane-1,2-diamine Drug Info [53]
(1R,2S)-1,2-diphenylethane-1,2-diamine Drug Info [53]
(2-(2-chlorophenyl)pyridin-3-yl)methanamine Drug Info [53]
(2-chloro-6-phenoxyphenyl)methanamine Drug Info [53]
(2s)-Pyrrolidin-2-Ylmethylamine Drug Info [54]
(3S,4R)-3-butyl-1-phenylpiperidin-4-amine Drug Info [55]
(5-phenyl-3H-benzo[d]imidazol-4-yl)methanamine Drug Info [56]
(R)-1-(2-aminoacetyl)pyrrolidin-2-ylboronic acid Drug Info [57]
(S)-2-Amino-1-azetidin-1-yl-2-cyclohexyl-ethanone Drug Info [58]
(S)-2-Amino-1-thiazolidin-3-yl-propane-1-thione Drug Info [59]
(S)-pyrrolidin-1-yl(pyrrolidin-2-yl)methanone Drug Info [60]
(S)-pyrrolidin-2-yl(thiazolidin-3-yl)methanone Drug Info [61]
1-(1-phenylcyclopentyl)methylamine Drug Info [62]
1-benzhydryl-3-butylpiperidin-4-amine Drug Info [55]
1-benzyl-4-(2,4-dichlorophenyl)pyrrolidin-3-amine Drug Info [63]
1-biphenyl-2-ylmethanamine Drug Info [62]
2-(2-chlorophenyl)-2-morpholinoethanamine Drug Info [53]
2-Amino-3-Methyl-1-Pyrrolidin-1-Yl-Butan-1-One Drug Info [64]
3-butyl-1-(naphthalen-1-yl)piperidin-4-amine Drug Info [55]
4-(2,4-dichlorophenyl)-1-phenylpyrrolidin-3-amine Drug Info [63]
4-(2,4-dichlorophenyl)-1-tosylpyrrolidin-3-amine Drug Info [63]
4-iodophenyl-alaninyl-(S)-2-cyano-pyrrolidine Drug Info [65]
ABT-279 Drug Info [14]
ABT-341 Drug Info [52]
Alogliptin Drug Info [14], [66], [67]
Alpha-D-Mannose Drug Info [64]
ALS 2-0426 Drug Info [68]
ASC-201 Drug Info [69]
ASP8497 Drug Info [14]
BPI-711001 Drug Info [69]
C-(2'-Chloro-biphenyl-2-yl)-methylamine Drug Info [53]
compound 1 (Xiao et al. 2014) Drug Info [69]
compound 24dd Drug Info [70]
Cyclohexylglycine-(2S)-cyanopyrrolidine Drug Info [71]
D-420720 Drug Info [69]
D-Val-L-boroPro Drug Info [72]
DA-1229 Drug Info [73]
DB-160 Drug Info [69]
Denagliptin Drug Info [14]
Diisopropylphosphono Group Drug Info [64]
Dipeptidyl peptidase IV inhibitors Drug Info [69]
DIPROTIN A Drug Info [74]
DPP-IV inhibitors Drug Info [69]
DPP-IV inhibitors Drug Info [69]
DPP-IV inhibitors Drug Info [69]
DSP-7238 Drug Info [69]
Dutogliptin Drug Info [75]
EMC-0901 Drug Info [69]
ER-319711-15 Drug Info [14]
FE 999011 Drug Info [76]
Fucose Drug Info [64]
Gemigliptin Drug Info [77]
IDDBCP161883 Drug Info [78], [14]
Iodo-Phenylalanine Drug Info [64]
IP10.C8-1 Drug Info [79], [28]
Isoleucine thiazolidide DPP IV Drug Info [14]
KR-62436 Drug Info [80]
L-Ala-L-boroPro Drug Info [72]
L-Val-L-boroPro Drug Info [72]
LC-150444 Drug Info [81]
Linagliptin Drug Info [14], [82]
LY-2463665 Drug Info [14]
Melogliptin Drug Info [14]
N-alkyl Gly-boro-Pro derivative Drug Info [83]
N-isoleucylthiazolidine Drug Info [71]
N4-(4-chlorobenzyl)-2,4-diaminobutanoylpiperidine Drug Info [84]
NVP-DPP728 Drug Info [85]
P32/98 Drug Info [31]
PK-44 Drug Info [69]
PSN-9301 Drug Info [86]
R-1438 Drug Info [14]
Retagliptin Drug Info [69]
Saxagliptin Drug Info [9], [14], [87]
Sitagliptin Drug Info [88], [89], [14], [90]
SSR-162369 Drug Info [14]
SYR-472 Drug Info [91], [67]
TA-6666 Drug Info [92]
TAK-100 Drug Info [67]
TRC-8XXX series Drug Info [69]
Trelagliptin Succinate Drug Info [69]
Vildagliptin Drug Info [14]
Modulator Anagliptin Drug Info [93]
ARI-2243 Drug Info [94]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride Drug Info [95]
E-3024 Drug Info
IP10 C8 Drug Info [28]
Kombiglyze XR/Komboglyze FDC Drug Info [69]
KRP-104 Drug Info [96]
MK-3102 Drug Info [97]
PF-00734200 Drug Info
PT-630 Drug Info [95]
SaxaDapa FDC Drug Info [24], [25]
Teneligliptin Drug Info [69]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Protein digestion and absorption
NetPath Pathway IL2 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
References
REF 12013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6319).
REF 3ClinicalTrials.gov (NCT02330406) Randomized Evaluation of Anagliptin Versus Sitagliptin On Low-density lipoproteiN Cholesterol in Diabetes Trial. U.S. National Institutes of Health.
REF 4Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 5Drugs@FDA (Edaravone)
REF 6KOMBIGLYZE? XR tablets approved in the US for the treatment of type 2 diabetes mellitus in adults
REF 7(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6318).
REF 8Clinical pipeline report, company report or official report of Boehringer Ingelheim.
REF 9Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
REF 10(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6316).
REF 112006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
REF 12FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022044.
REF 13(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6286).
REF 14Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
REF 15(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6310).
REF 16ClinicalTrials.gov (NCT00690638) Safety and Efficacy Study of Dutogliptin/PHX1149T to Treat Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
REF 17ClinicalTrials.gov (NCT01990469) Efficacy and Safety of Gemigliptin 50mg qd Added in Patients With Type 2 Diabetes Inadequately Controlled on Glimepiride and Metformin. U.S. National Institutes of Health.
REF 18ClinicalTrials.gov (NCT01798238) Teneligliptin(MP-513) Versus Placebo in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
REF 19ClinicalTrials.gov (NCT02089126) Phase III Trial to Evaluate the Efficacy and Safety of Gemigliptin 50mg qd Added to Ongoing Glimepiride as Fix-dose Combination in Patients With Type 2 Diabetes. U.S.National Institutes of Health.
REF 20ClinicalTrials.gov (NCT01703208) A Study to Assess Cardiovascular Outcomes Following Treatment With MK-3102 in Participants With Type 2 Diabetes Mellitus (MK-3102-018). U.S. National Institutes of Health.
REF 21(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8402).
REF 22ClinicalTrials.gov (NCT02411084) Study of BEGEDINA vs "Conventional Treatment" for Treating Steroid-Resistant Acute GvHD. U.S. National Institutes of Health.
REF 23(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8691).
REF 24Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes. Cardiol Rev. 2010 Jul-Aug;18(4):213-7.
REF 25The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab. 2010 Nov;12(11):1004-12.
REF 26Clinical pipeline report, company report or official report of Takeda.
REF 27ClinicalTrials.gov (NCT00387972) Study Of Denagliptin In Subjects With Type 2 Diabetes Mellitus (T2DM). U.S. National Institutes of Health.
REF 28Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune functions. Clin Chem Lab Med. 2009;47(3):253-61.
REF 29ClinicalTrials.gov (NCT00525330) A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of KRP-104 in Patients With Type 2 Diabetes Inadequately Controlled on Metformin Alone. U.S. National Institutes of Health.
REF 30Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021640)
REF 31Long-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.
REF 32ClinicalTrials.gov (NCT00473525) 12 Week Study Of PF-00734200 For The Treatment Of Type 2 Diabetes Mellitus In Subjects Treated With Metformin. U.S. National Institutes of Health.
REF 33(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7413).
REF 34Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031210)
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028500)
REF 36ClinicalTrials.gov (NCT00961025) A Study to Characterize the Pharmacokinetics/Pharmacodynamics and Effect of Food of DA-1229 in Healthy Male Subjects. U.S. National Institutes of Health.
REF 37ClinicalTrials.gov (NCT02449330) Teneligliptin on the Progressive Left Ventricular Diastolic Dysfunction With Type 2 Diabetes Mellitus Study.
REF 38ASP8497 is a novel selective and competitive dipeptidyl peptidase-IV inhibitor with antihyperglycemic activity. Biochem Pharmacol. 2008 Jul 1;76(1):98-107.
REF 397-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one is a novel competitive and selective inhibitor of dipeptidyl peptidase IV with an antihyperglycemic activity. J Pharmacol Exp Ther. 2006 Dec;319(3):1253-7. Epub 2006 Sep 15.
REF 40Discovery 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. 2012 Oct 1;20(19):5705-19.
REF 41Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022304)
REF 42Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014308)
REF 43Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012640)
REF 44Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019065)
REF 45Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018193)
REF 46Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020875)
REF 47Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025075)
REF 48Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022199)
REF 49Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028364)
REF 50Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028616)
REF 51Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022168)
REF 52J Med Chem. 2006 Nov 2;49(22):6439-42.Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
REF 53Bioorg Med Chem Lett. 2006 Mar 1;16(5):1405-9.In silico fragment-based discovery of DPP-IV S1 pocket binders.
REF 54DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
REF 55Bioorg Med Chem Lett. 2007 Jun 1;17(11):2966-70. Epub 2007 Mar 25.1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors.
REF 56Bioorg Med Chem Lett. 2008 Apr 1;18(7):2362-7. Epub 2008 Mar 4.Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.
REF 57J Med Chem. 2008 Oct 9;51(19):6005-13. Epub 2008 Sep 11.Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety.
REF 58Bioorg Med Chem Lett. 2005 Nov 1;15(21):4770-3.New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors.
REF 59Bioorg Med Chem Lett. 2002 Oct 21;12(20):2825-8.Development of potent and selective dipeptidyl peptidase II inhibitors.
REF 60Bioorg Med Chem. 2008 Feb 15;16(4):1613-31. Epub 2007 Nov 17.Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group.
REF 61Bioorg Med Chem Lett. 2007 May 1;17(9):2618-21. Epub 2007 Feb 8.[(S)-gamma-(4-Aryl-1-piperazinyl)-l-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors.
REF 62The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 63Bioorg Med Chem Lett. 2007 Apr 1;17(7):2005-12. Epub 2007 Jan 19.Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.
REF 64How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 65Bioorg Med Chem Lett. 2006 Jan 1;16(1):123-8. Epub 2005 Oct 19.Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors.
REF 66Combining a dipeptidyl peptidase-4 inhibitor, alogliptin, with pioglitazone improves glycaemic control, lipid profiles and beta-cell function in db/db mice. Br J Pharmacol. 2009 Jun;157(3):415-26. Epub 2009 Apr 3.
REF 67Clinical pipeline report, company report or official report of Takeda (2009).
REF 68Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes. Pharmacological Reviews April 2012 vol. 64 no. 2 188-237.
REF 69(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1612).
REF 70Discovery 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.
REF 71J Med Chem. 2006 Jan 12;49(1):373-80.2-[3-[2-[(2S)-2-Cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]- 1,2,3,4-tetrahydroisoquinoline: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV.
REF 72J Med Chem. 2007 May 17;50(10):2391-8. Epub 2007 Apr 26.Synthesis and characterization of constrained peptidomimetic dipeptidyl peptidase IV inhibitors: amino-lactam boroalanines.
REF 73DA-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.
REF 74Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. Epub 2007 Dec 3.Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin.
REF 75Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. Diabetes Obes Metab. 2010 Apr;12(4):348-55.
REF 76Chronic 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.
REF 77Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects. Curr Med Res Opin. 2015 Feb;31(2):229-41.
REF 78Teneligliptin: a DPP-4 inhibitor for the treatment of type 2 diabetes. Diabetes Metab Syndr Obes. 2013 May 6;6:187-95.
REF 79ClinicalTrials.gov (NCT00824980) Combined Inhibition of Dipeptidyl Peptidase IV (DPIV/CD26) and Aminopeptidase N (APN/CD13) in the Treatment of Psoriasis. U.S. National Institutes of Health.
REF 80Bioorg Med Chem. 2009 Mar 1;17(5):1783-802. Epub 2009 Jan 31.Medicinal chemistry approaches to the inhibition of dipeptidyl peptidase-4 for the treatment of type 2 diabetes.
REF 81Clinical pipeline report, company report or official report of ShangHai APIs Chemical.
REF 82Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
REF 83Bioorg Med Chem Lett. 2005 Oct 1;15(19):4239-42.Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.
REF 84Bioorg Med Chem Lett. 2006 Sep 15;16(18):4777-9. Epub 2006 Jul 17.Synthesis and dipeptidyl peptidase inhibition of N-(4-substituted-2,4-diaminobutanoyl)piperidines.
REF 85Eur J Med Chem. 2008 Aug;43(8):1603-11. Epub 2007 Nov 29.A three-dimensional pharmacophore model for dipeptidyl peptidase IV inhibitors.
REF 86Navigating the chemical space of dipeptidyl peptidase-4 inhibitors. Drug Des Devel Ther. 2015; 9: 4515-4549.
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REF 88Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and changes of dipeptidyl peptidase IV mRNA levels during cell differentiation. J Biol Chem. 1992 Mar 5;267(7):4824-33.
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