Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDIGC1)

• DTT Name: Dipeptidyl peptidase 4 (DPP-4)
• Synonyms: Tcell activation antigen CD26; TP103; T-cell activation antigen CD26; Dipeptidyl peptidase IV; Dipeptidyl peptidase 4 soluble form; DPP-IV; DPP IV; DPP 4; CD26; Adenosine deaminase complexing protein-2; Adenosine deaminase complexing protein 2; ADCP2; ADCP-2; ADABP
• Gene Name: DPP4
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: DPP4_HUMAN
• TTD ID: T31391
• EC Number: EC 3.4.14.5
• Sequence:
  MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
  RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY
  VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL
  PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF
  YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL
  CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS
  EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN
  EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY
  TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY
  PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT
  FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE
  YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS
  KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP
• Function: 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 promotion of 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. Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) (R-HSA-400511)
  Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771)

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alogliptin	DM8WI3R	Type-2 diabetes	5A11	Approved	[1]
Anagliptin	DMJXIC9	Type-2 diabetes	5A11	Approved	[2]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride	DM34TXO	Type-2 diabetes	5A11	Approved	[3]
Linagliptin	DMWFJTR	Non-insulin dependent diabetes	5A11	Approved	[4]
Saxagliptin	DMGXENV	Type-2 diabetes	5A11	Approved	[5]
Sitagliptin	DMGDKXN	Cystic fibrosis	CA25	Approved	[6]
Vildagliptin	DMYN59P	Type-2 diabetes	5A11	Approved	[7]

20 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dutogliptin	DMM5VTA	Type-2 diabetes	5A11	Phase 3	[8]
Gemigliptin	DMZKGPV	Diabetic complication	5A2Y	Phase 3	[9]
IDDBCP161883	DMV3DHQ	Type-2 diabetes	5A11	Phase 3	[10]
LC-150444	DM09RKB	Type-2 diabetes	5A11	Phase 3	[11]
MK-3102	DM3PSUF	Type-2 diabetes	5A11	Phase 3	[12]
SAND-26	DMKHLRT	Autoimmune diabetes	5A10	Phase 3	[13]
SaxaDapa FDC	DMAPRWV	Diabetic complication	5A2Y	Phase 3	[14]
SYR-472	DM9L1AC	Metabolic disorder	5C50-5D2Z	Phase 3	[15]
Denagliptin	DMZV3SY	Type-2 diabetes	5A11	Phase 2/3	[7]
IP10 C8	DMANRGW	Psoriasis vulgaris	EA90	Phase 2	[16]
KRP-104	DMQDLVW	Type-2 diabetes	5A11	Phase 2	[17]
Melogliptin	DMVJ6WS	Type-2 diabetes	5A11	Phase 2	[7]
P32/98	DMW1OI6	Autism spectrum disorder	6A02	Phase 2	[18]
PF-00734200	DMNM4CK	Type-2 diabetes	5A11	Phase 2	[19]
YSCMA	DMIA9JD	Haematological malignancy	2B33.Y	Phase 1/2	[20]
ARI-2243	DMN4D3A	Type-2 diabetes	5A11	Phase 1	[21]
DA-1229	DM4OTWL	Type-2 diabetes	5A11	Phase 1	[22]
REC-01	DM25GIA	Acute myocardial infarction	BA41	Phase 1	[23]
Teneligliptin	DMGJCDR	Type-2 diabetes	5A11	Phase 1	[24]
ZYDPLA 1	DMU2D0B	Type-2 diabetes	5A11	Phase 1	[25]

54 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminopiperidine derivative 1	DMFKTJL	N. A.	N. A.	Patented	[26]
Aminopiperidine derivative 2	DM4JDHO	N. A.	N. A.	Patented	[26]
Beta-phe compound 1	DM8D3FG	N. A.	N. A.	Patented	[26]
Beta-phe compound 2	DM786OD	N. A.	N. A.	Patented	[26]
Beta-phe compound 3	DM0G8XP	N. A.	N. A.	Patented	[26]
Dihydropyrrolopyrazole derivative 1	DMHGE1T	N. A.	N. A.	Patented	[26]
Imidazo cyclohexylamine derivative 1	DM34ZCG	N. A.	N. A.	Patented	[26]
Imidazo cyclohexylamine derivative 2	DMKPAN3	N. A.	N. A.	Patented	[26]
Imidazo cyclohexylamine derivative 3	DMCQBZK	N. A.	N. A.	Patented	[26]
Imidazo pyridine derivative 2	DMC49SV	N. A.	N. A.	Patented	[26]
Peptide analog 44	DMOJDQF	N. A.	N. A.	Patented	[26]
Peptide analog 45	DMGA3U8	N. A.	N. A.	Patented	[26]
Peptide analog 46	DMC48AX	N. A.	N. A.	Patented	[26]
Peptide analog 47	DM7U8WD	N. A.	N. A.	Patented	[26]
Peptide analog 48	DMM2WA4	N. A.	N. A.	Patented	[26]
Peptide analog 49	DMP5SA2	N. A.	N. A.	Patented	[26]
Peptide analog 50	DMM8K7R	N. A.	N. A.	Patented	[26]
Peptide analog 51	DM1D7CE	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-11	DMQB4LE	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-12	DM8JIDR	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-13	DMBS2FT	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-14	DMC82UR	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-15	DMO913H	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-16	DMIFVXE	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-17	DMY4AJ7	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-18	DM0W5UA	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-21	DM2W9AP	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-34	DMX5R9N	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-37	DMMZO8Y	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-38	DMJOPEL	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-50	DMMLJ5E	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-52	DMDLPB7	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-56	DMB3DMR	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-6	DM03UK2	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-69	DMPY8NU	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-70	DMEYLM2	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-71	DMZB140	N. A.	N. A.	Patented	[26]
PMID25482888-Compound-72	DMQOVKF	N. A.	N. A.	Patented	[26]
Pyrimidine derivative 30	DMTQBUD	N. A.	N. A.	Patented	[26]
Pyrimidine derivative 31	DMOJTLU	N. A.	N. A.	Patented	[26]
Pyrimidine derivative 32	DMCUQFG	N. A.	N. A.	Patented	[26]
Pyrimidine derivative 33	DMWL5V0	N. A.	N. A.	Patented	[26]
Pyrimidinedione derivative 1	DML4OYQ	N. A.	N. A.	Patented	[26]
Pyrrolo[1,2-f]triazine derivative 1	DMI0AW7	N. A.	N. A.	Patented	[26]
Pyrrolo[1,2-f]triazine derivative 2	DM7DU9P	N. A.	N. A.	Patented	[26]
Quinazoline derivative 1	DMOBFAU	N. A.	N. A.	Patented	[26]
Thiomorpholine derivative 1	DMZP6KR	N. A.	N. A.	Patented	[26]
Thiomorpholine derivative 2	DMWOK1D	N. A.	N. A.	Patented	[26]
Triazole piperazine derivative 1	DMPRGLZ	N. A.	N. A.	Patented	[26]
Triazolo-pyrimidinedione derivative 1	DMJN72E	N. A.	N. A.	Patented	[26]
Triazolo-pyrimidinedione derivative 2	DMLGNB2	N. A.	N. A.	Patented	[26]
Tricyclic heterocycle derivative 6	DMQJK70	N. A.	N. A.	Patented	[26]
Xanthine derivative 1	DMIULVJ	N. A.	N. A.	Patented	[26]
Xanthine/amino piperidine compound 1	DMNXJ8G	N. A.	N. A.	Patented	[26]

10 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ALS 2-0426	DMEKHX0	Type-2 diabetes	5A11	Discontinued in Phase 2	[27]
NVP-DPP728	DM9HKOM	Type-2 diabetes	5A11	Discontinued in Phase 2	[28]
PSN-9301	DMMF9RS	Diabetic complication	5A2Y	Discontinued in Phase 2	[29]
R-1438	DM2Q5IS	Type-2 diabetes	5A11	Discontinued in Phase 2	[7]
TA-6666	DMB3W20	Type-2 diabetes	5A11	Discontinued in Phase 2	[30]
ABT-279	DMWVFDH	Type-2 diabetes	5A11	Discontinued in Phase 1	[7]
SSR-162369	DMI3K2D	Type-2 diabetes	5A11	Discontinued in Phase 1	[7]
TAK-100	DMH16ND	Diabetic complication	5A2Y	Discontinued in Phase 1	[1]
DSP-7238	DMAE43P	Diabetic complication	5A2Y	Terminated	[24]
PT-630	DMH3RPO	Type-2 diabetes	5A11	Terminated	[3]

4 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP8497	DMRPX4W	Type-2 diabetes	5A11	Preclinical	[7]
ER-319711-15	DMBINP0	Type-2 diabetes	5A11	Preclinical	[7]
LY-2463665	DM7XPDB	Type-2 diabetes	5A11	Preclinical	[7]
PT630	DM9SY8E	Colon cancer	2B90.Z	Preclinical	[31]

47 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-6-(2-chlorophenyl)cyclohex-3-enamine	DM23W58	Discovery agent	N.A.	Investigative	[32]
(1-phenylcyclopentyl)methanamine	DM0TUKZ	Discovery agent	N.A.	Investigative	[33]
(1R,2R)-1,2-diphenylethane-1,2-diamine	DM18E9D	Discovery agent	N.A.	Investigative	[34]
(1R,2S)-1,2-diphenylethane-1,2-diamine	DM28D9E	Discovery agent	N.A.	Investigative	[34]
(2-(2-chlorophenyl)pyridin-3-yl)methanamine	DMYOTMP	Discovery agent	N.A.	Investigative	[34]
(2-chloro-6-phenoxyphenyl)methanamine	DMOS864	Discovery agent	N.A.	Investigative	[34]
(2s)-Pyrrolidin-2-Ylmethylamine	DMZON3T	Discovery agent	N.A.	Investigative	[35]
(3S,4R)-3-butyl-1-phenylpiperidin-4-amine	DMAEXO3	Discovery agent	N.A.	Investigative	[36]
(5-phenyl-3H-benzo[d]imidazol-4-yl)methanamine	DM2HCUK	Discovery agent	N.A.	Investigative	[37]
(R)-1-(2-aminoacetyl)pyrrolidin-2-ylboronic acid	DMGD026	Discovery agent	N.A.	Investigative	[38]
(S)-2-Amino-1-azetidin-1-yl-2-cyclohexyl-ethanone	DMWBH9N	Discovery agent	N.A.	Investigative	[39]
(S)-2-Amino-1-thiazolidin-3-yl-propane-1-thione	DMORFZE	Discovery agent	N.A.	Investigative	[40]
(S)-pyrrolidin-1-yl(pyrrolidin-2-yl)methanone	DMXVQJI	Discovery agent	N.A.	Investigative	[41]
(S)-pyrrolidin-2-yl(thiazolidin-3-yl)methanone	DM16N7Z	Discovery agent	N.A.	Investigative	[42]
1-benzhydryl-3-butylpiperidin-4-amine	DMBAZG3	Discovery agent	N.A.	Investigative	[36]
1-benzyl-4-(2,4-dichlorophenyl)pyrrolidin-3-amine	DMGDY4X	Discovery agent	N.A.	Investigative	[43]
1-biphenyl-2-ylmethanamine	DMKJYCU	Discovery agent	N.A.	Investigative	[33]
2-(2-chlorophenyl)-2-morpholinoethanamine	DMFG2S5	Discovery agent	N.A.	Investigative	[34]
2-Amino-3-Methyl-1-Pyrrolidin-1-Yl-Butan-1-One	DM6AYDL	Discovery agent	N.A.	Investigative	[44]
3-butyl-1-(naphthalen-1-yl)piperidin-4-amine	DMXF8M0	Discovery agent	N.A.	Investigative	[36]
4-(2,4-dichlorophenyl)-1-phenylpyrrolidin-3-amine	DMCGOPQ	Discovery agent	N.A.	Investigative	[43]
4-(2,4-dichlorophenyl)-1-tosylpyrrolidin-3-amine	DMRMAOI	Discovery agent	N.A.	Investigative	[43]
4-iodophenyl-alaninyl-(S)-2-cyano-pyrrolidine	DMJMOAI	Discovery agent	N.A.	Investigative	[45]
ABT-341	DMZ3YTO	Discovery agent	N.A.	Investigative	[32]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[44]
ASC-201	DM5WR0L	Bone marrow transplantation	QB63.6	Investigative	[24]
BPI-711001	DMOSG0Q	Hypoglycemia	5A41	Investigative	[24]
C-(2'-Chloro-biphenyl-2-yl)-methylamine	DMNMYWI	Discovery agent	N.A.	Investigative	[34]
Cyclohexylglycine-(2S)-cyanopyrrolidine	DMNG4B1	Discovery agent	N.A.	Investigative	[46]
D-420720	DM048OG	Diabetic complication	5A2Y	Investigative	[24]
D-Val-L-boroPro	DML4G6K	Discovery agent	N.A.	Investigative	[47]
DB-160	DMEST0R	Non-insulin dependent diabetes	5A11	Investigative	[24]
Diisopropylphosphono Group	DMND2AS	Discovery agent	N.A.	Investigative	[44]
DIPROTIN A	DMGBCP0	Discovery agent	N.A.	Investigative	[48]
E-3024	DME5JBH	Discovery agent	N.A.	Investigative	[49]
EMC-0901	DMUH1JX	Diabetic complication	5A2Y	Investigative	[24]
FE 999011	DMKVA6Z	Discovery agent	N.A.	Investigative	[50]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[44]
Iodo-Phenylalanine	DMF8EJ6	Discovery agent	N.A.	Investigative	[44]
KR-62436	DM7G8KR	Non-insulin dependent diabetes	5A11	Investigative	[51]
L-Ala-L-boroPro	DMH6XTP	Discovery agent	N.A.	Investigative	[47]
L-Val-L-boroPro	DMPGT80	Discovery agent	N.A.	Investigative	[47]
N-isoleucylthiazolidine	DM53AS0	Discovery agent	N.A.	Investigative	[46]
N4-(4-chlorobenzyl)-2,4-diaminobutanoylpiperidine	DMARZHU	Discovery agent	N.A.	Investigative	[52]
PK-44	DM40HWI	Non-insulin dependent diabetes	5A11	Investigative	[24]
PMID20684603C24dd	DMWZK9U	Discovery agent	N.A.	Investigative	[53]
Retagliptin	DMQFSI5	Non-insulin dependent diabetes	5A11	Investigative	[24]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	5.40E-02	8.70E-03	1.20E-02
Type 2 diabetes	5A11	Liver tissue	9.54E-01	-0.27	-1.85

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Dipeptidyl peptidase IV (DPP4) DME Info
• Gene Name: DPP4

3 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Exenatide	DMYHBKN	Inflammation	1A00-CA43.1	Approved	[54]
Liraglutide	DM3FXPS	Non-insulin dependent diabetes	5A11	Approved	[55]
Semaglutide	DMAGFOD	Type-2 diabetes	5A11	Approved	[56]

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