DPP4

Summary

DPP4 (dipeptidyl peptidase 4, HGNC:3009) is a protein-coding gene on chromosome 2q24.2, encoding Dipeptidyl peptidase 4 (P27487). Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation.

The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19.

Source: NCBI Gene 1803 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 150 total — 1 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 33 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3009
Approved symbol	DPP4
Name	dipeptidyl peptidase 4
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	DPPIV
Ensembl gene	ENSG00000197635
Ensembl biotype	protein_coding
OMIM	102720
Entrez	1803

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 9 retained_intron, 8 nonsense_mediated_decay, 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000360534, ENST00000413651, ENST00000416189, ENST00000434918, ENST00000461836, ENST00000468903, ENST00000490286, ENST00000491591, ENST00000494507, ENST00000497461, ENST00000676479, ENST00000676624, ENST00000676768, ENST00000676810, ENST00000676996, ENST00000677015, ENST00000677212, ENST00000678522, ENST00000678566, ENST00000678583, ENST00000678668, ENST00000678740, ENST00000679104, ENST00000881342, ENST00000881343

RefSeq mRNA: 4 — MANE Select: NM_001935 NM_001379604, NM_001379605, NM_001379606, NM_001935

CCDS: CCDS2216, CCDS92882

Canonical transcript exons

ENST00000360534 — 26 exons

Exon	Start	End
ENSE00001420909	161992245	161993384
ENSE00001428031	162073976	162074215
ENSE00003469885	162017108	162017155
ENSE00003472853	162018729	162018850
ENSE00003508024	162020581	162020688
ENSE00003514636	161994961	161995034
ENSE00003524201	162019223	162019276
ENSE00003525327	162045532	162045612
ENSE00003537896	162038949	162039021
ENSE00003555173	162020229	162020296
ENSE00003557301	162038302	162038422
ENSE00003577268	162011793	162011987
ENSE00003578186	162035164	162035324
ENSE00003589684	161995300	161995372
ENSE00003590541	162046915	162047006
ENSE00003594714	162033541	162033653
ENSE00003597566	162039132	162039184
ENSE00003605030	162009241	162009295
ENSE00003610376	162022755	162022799
ENSE00003623432	162014396	162014465
ENSE00003640971	162047403	162047501
ENSE00003641984	162005745	162005809
ENSE00003643951	162016768	162016866
ENSE00003650638	162024804	162024939
ENSE00003672736	162073399	162073486
ENSE00003678443	162008562	162008661

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2200 / max 926.2571, expressed in 1173 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31520	5.4911	837
31523	4.2255	782
31518	2.4864	650
31521	2.0881	462
31519	1.2992	492
31522	0.5043	249
31524	0.4916	262
31529	0.4781	205
31525	0.3196	135
31516	0.3054	170

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.65	gold quality
jejunal mucosa	UBERON:0000399	98.32	gold quality
parotid gland	UBERON:0001831	98.29	gold quality
tendon of biceps brachii	UBERON:0008188	98.13	gold quality
tendon	UBERON:0000043	97.48	gold quality
duodenum	UBERON:0002114	95.67	gold quality
nephron tubule	UBERON:0001231	95.62	gold quality
placenta	UBERON:0001987	94.00	gold quality
stromal cell of endometrium	CL:0002255	92.62	gold quality
parietal pleura	UBERON:0002400	92.59	gold quality
seminal vesicle	UBERON:0000998	92.06	gold quality
pleura	UBERON:0000977	91.04	gold quality
renal glomerulus	UBERON:0000074	90.61	gold quality
metanephric glomerulus	UBERON:0004736	90.18	gold quality
adult mammalian kidney	UBERON:0000082	89.82	gold quality
visceral pleura	UBERON:0002401	89.80	gold quality
skin of hip	UBERON:0001554	89.59	gold quality
kidney	UBERON:0002113	89.30	gold quality
kidney epithelium	UBERON:0004819	89.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.80	gold quality
small intestine	UBERON:0002108	88.70	gold quality
rectum	UBERON:0001052	88.53	gold quality
cortex of kidney	UBERON:0001225	87.75	gold quality
synovial joint	UBERON:0002217	87.65	gold quality
germinal epithelium of ovary	UBERON:0001304	87.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.97	gold quality
colonic epithelium	UBERON:0000397	86.18	gold quality
metanephros	UBERON:0000081	86.05	gold quality
prostate gland	UBERON:0002367	86.03	gold quality
liver	UBERON:0002107	86.01	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	256.74
E-GEOD-81608	yes	132.47
E-MTAB-5061	yes	29.80
E-HCAD-10	yes	27.87
E-GEOD-81547	yes	20.26
E-ENAD-27	yes	11.73
E-GEOD-83139	yes	10.33
E-GEOD-124858	no	173.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, HNF1A, HNF1B, MYC, USF1, USF2

Literature-anchored findings (GeneRIF, showing 40)

• Soluble CD26 induces T cell proliferation in Antigen presenting cells (PMID:11739489)
• Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans (PMID:11773049)
• DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema. (PMID:11882590)
• Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. (PMID:11901152)
• expression of the seprase-DPPIV complex is restricted to migratory cells involved in wound closure (PMID:12023964)
• Decrease of serum dipeptidylpeptidase activity in severe sepsis patients: relationship to procalcitonin. (PMID:12031601)
• chromogranin B(586-602) peptide can serve as a substrate for the lymphocyte surface glycoprotein CD26, also known as dipeptidyl peptidase IV (DPP IV), generating a new peptide ER-15 (CgB(588-602)) (PMID:12047913)
• DPIV mediated transcellular proteolysis (PMID:12095981)
• galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules (PMID:12112826)
• CD26 interferes with transduction pathway(s) needed for the maturation of T cells and plays an important role in T lymphocyte homeostasis in peripheral blood. (PMID:12175726)
• examination of expression and enzymatic activity in recipients of kidney allografts (PMID:12176563)
• Involvement in extravillous trophoblast invasion and differentiation (PMID:12213886)
• Increased expression in human mesothelial cells by malignant ascites from ovarian carcinoma patients (PMID:12239451)
• REVIEW: expression and effects on immune cells (PMID:12437097)
• The process of CXCL12/SDF-1 alpha cleavage by CD26/DPPIV on a subpopulation of cord blood CD34+ cells represents a novel regulatory mechanism in hemopoietic stem and progenitor cells for the migration, homing, and mobilization of these cells. (PMID:12471135)
• The CD26 structure indicates how substrate specificity is achieved and reveals a new and unexpected opening to the active site. (PMID:12483204)
• catalytic properties and inhibition of this proline-specific enzyme (PMID:12529175)
• Review. CD26 has an essential role in human T-cell activation, as well as its ability to regulate the biological effects of selected chemokines through its DPPIV activity. (PMID:12579300)
• crystals of dipeptidylpeptidase IV belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 118.04, b = 125.92, c = 136.84 A, and diffracts beyond 2.6 A resolution (PMID:12595736)
• Expressed in normal endometrial glandular cells, but expression in endometrial adenocarcinoma is down-regulated with increasing grade. Regulatory role in neoplastic transformation and progression of endometrial adenocarcinomas. (PMID:12634639)
• report the structure of human dipeptidyl peptidase IV especially focusing on a unique eight-bladed beta-propeller domain; discuss the way for the access of the substrate to this domain (PMID:12646248)
• an examination of the substrate specificity of this enzyme (REVIEW) (PMID:12675218)
• The active site of this enzyme is examined and compared with Porphyromonas gingivalis. (PMID:12675220)
• The kinetics of this enzyme are examined, after cloning in Pichia pastoris. (PMID:12675229)
• Protein-protein interactions dependent on this enzyme are investigated using surface plasmon resonance. (PMID:12675231)
• This protein acts synergistically with APN to regulate T cell function. (PMID:12675232)
• An increase in this enzyme is associated with graft rejection. Inhibition of this enzyme prevents kieney graft rejection. (PMID:12675233)
• plays a role in the digestion of an immunodominant epitope in celiac disease (PMID:12675238)
• This enzyme is expressed in cutaneous infiltrates from patients with cutaneous T-cell lymphoma. (PMID:12675243)
• This enzyme is expressed in endometrial adenocarcinoma and is negatively correlated with tumor grade. (PMID:12675245)
• Adhesion to mesothelial is increased by overexpression of dipeptidyl peptidase IV. (PMID:12675246)
• This enzyme suppresses ovarian carcinoma in peritoneal dissemination in vitro and in vivo. (PMID:12675247)
• This enzyme is active in prostatic secretions and prostate cancer. (PMID:12675248)
• This enzyme is a marker of mood in anorexia nervosa and bulimia nervosa patients. (PMID:12675253)
• Serum levels are decreased in patients with Crohn and inflammatory bowel disease who are clinically depressed. (PMID:12675254)
• elevated serum levels in chronic hepatitis C and other viral infections suggest that this activity originates not only from the liver, but also from other sources such as peripheral blood cells involved in the control of viral infections. (PMID:12727530)
• Increased adhesion of ovarian carcinoma cells to mesothelial cells by overexpression of dipeptidyl peptidase IV. (PMID:12767062)
• This enzyme is a marker in thyroid tumors. (PMID:12820316)
• structure of the binary complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine has been solved, revealing the nature of the covalent interaction with the active-site serine (PMID:12832764)
• strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible for the attenuation of T-cell activation signaling through CD26 (PMID:14525771)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:136971	ENSDARG00000055970
danio_rerio	dpp4	ENSDARG00000079420
mus_musculus	Dpp4	ENSMUSG00000035000
rattus_norvegicus	Dpp4	ENSRNOG00000030763
drosophila_melanogaster	ome	FBGN0259175
caenorhabditis_elegans		WBGENE00001054

Paralogs (6): DPP8 (ENSG00000074603), FAP (ENSG00000078098), DPP6 (ENSG00000130226), DPP9 (ENSG00000142002), APEH (ENSG00000164062), DPP10 (ENSG00000175497)

Protein

Protein identifiers

Dipeptidyl peptidase 4 — P27487 (reviewed: P27487)

Alternative names: ADABP, Adenosine deaminase complexing protein 2, Dipeptidyl peptidase IV, T-cell activation antigen CD26, TP103

All UniProt accessions (9): A0A7I2V2I2, A0A7I2V2R5, A0A7I2V2X8, A0A7I2V3F5, A0A7I2V501, A0A7I2V5R8, F8WBB6, F8WE17, P27487

UniProt curated annotations — full annotation on UniProt →

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 promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Also acts 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 such as brain natriuretic peptide 32. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. (Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2.

Subunit / interactions. Monomer. Homodimer. Heterodimer with Seprase (FAP). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes. Interacts (via extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct. Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3. Interacts with human coronavirus-EMC spike protein and acts as a receptor for this virus. (Microbial infection) Interacts with MERS coronavirus/MERS-CoV spike protein.

Subcellular location. Secreted Cell membrane. Apical cell membrane. Cell projection. Invadopodium membrane. Lamellipodium membrane. Cell junction. Membrane raft.

Tissue specificity. Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon.

Post-translational modifications. The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane form also named MDPP) by proteolytic processing. N- and O-Glycosylated. Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation.

Activity regulation. Inhibited by GPC3 and diprotin A.

Domain organisation. The extracellular cysteine-rich region is necessary for association with collagen, dimer formation and optimal dipeptidyl peptidase activity.

Induction. Up-regulated by IL12/interleukin-12 on activated T-cells. IL12-activated cells expressed enhanced levels of DPP4 but not mRNAs. Down-regulated by TNF. Up-regulated in migratory endothelial cells and in the invasive endothelial cells in tumors. Induced by hypoxia.

Miscellaneous. Level of plasma concentrations of the soluble form (SDPP) can be managed as a colon carcinoma diagnostic and prognostic marker.

Similarity. Belongs to the peptidase S9B family. DPPIV subfamily.

RefSeq proteins (4): NP_001366533, NP_001366534, NP_001366535, NP_001926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001375	Peptidase_S9_cat	Domain
IPR002469	Peptidase_S9B_N	Domain
IPR002471	Pept_S9_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050278	Serine_Prot_S9B/DPPIV	Family

Pfam: PF00326, PF00930

Enzyme classification (BRENDA):

• EC 3.4.14.5 — dipeptidyl-peptidase IV (BRENDA: 38 organisms, 518 substrates, 2236 inhibitors, 199 Km, 147 kcat entries)

Substrate kinetics (BRENDA)

105 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLY-PRO-4-NITROANILIDE	0.06–44.08	34
ALA-PRO-7-AMIDO-4-METHYLCOUMARIN	0.0003–0.022	11
ALA-PRO-7-AMIDO-4-TRIFLUOROMETHYLCOUMARIN	0.013–0.015	10
GLY-PRO-P-NITROANILIDE	0.05–3.1	9
GLY-PRO-7-AMIDO-4-METHYLCOUMARIN	0.0069–0.57	8
GLY-L-PRO-4-NITROANILIDE	0.076–0.3	5
ALA-PRO-7-AMIDO-4-TRIFLUOROMETHYL COUMARIN	0.0148–0.0172	3
LYS-PRO-7-AMIDO-4-METHYLCOUMARIN	0.0001–0.035	3
ALA-ALA-2-NAPHTHYLAMIDE	0.82–1	2
GLU-PRO-7-AMIDO-4-METHYLCOUMARIN	0.003–0.457	2
GLY-L-PRO-7-AMIDO-4-METHYLCOUMARIN	0.0046–0.0194	2
GLY-L-PRO-RHODAMINE 110-(N-PENTYL)MALEIMIDE	0.0013	2
GLY-PRO-4-METHOXY-BETA-NAPHTHYLAMIDE	0.5–1	2
L-ALA-L-PRO-4-NITROANILIDE	0.06–0.4	2
L-ALA-L-PRO-P-NITROANILIDE	0.099–0.432	2

UniProt features (132 total): strand 61, helix 18, mutagenesis site 13, turn 12, glycosylation site 9, disulfide bond 5, sequence conflict 5, active site 3, chain 2, topological domain 2, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

117 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4A5S	X-RAY DIFFRACTION	1.62
4N8D	X-RAY DIFFRACTION	1.65
5T4B	X-RAY DIFFRACTION	1.76
5T4E	X-RAY DIFFRACTION	1.77
6B1E	X-RAY DIFFRACTION	1.77
1PFQ	X-RAY DIFFRACTION	1.9
4PNZ	X-RAY DIFFRACTION	1.9
5T4F	X-RAY DIFFRACTION	1.9
6B1O	X-RAY DIFFRACTION	1.91
5I7U	X-RAY DIFFRACTION	1.95
9LBT	X-RAY DIFFRACTION	1.99
1TK3	X-RAY DIFFRACTION	2
2BGR	X-RAY DIFFRACTION	2
2G63	X-RAY DIFFRACTION	2
3D4L	X-RAY DIFFRACTION	2
3EIO	X-RAY DIFFRACTION	2
3HAC	X-RAY DIFFRACTION	2
3SWW	X-RAY DIFFRACTION	2
5ISM	X-RAY DIFFRACTION	2
3C45	X-RAY DIFFRACTION	2.05
1NU6	X-RAY DIFFRACTION	2.1
1R9M	X-RAY DIFFRACTION	2.1
1X70	X-RAY DIFFRACTION	2.1
2OGZ	X-RAY DIFFRACTION	2.1
2QT9	X-RAY DIFFRACTION	2.1
3HAB	X-RAY DIFFRACTION	2.1
3VJM	X-RAY DIFFRACTION	2.1
2IIV	X-RAY DIFFRACTION	2.15
1RWQ	X-RAY DIFFRACTION	2.2
1U8E	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27487-F1	96.45	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 630 (charge relay system); 708 (charge relay system); 740 (charge relay system)

Disulfide bonds (5): 328–339, 385–394, 444–447, 454–472, 649–762

Glycosylation sites (9): 150, 219, 229, 281, 321, 520, 685, 85, 92

Mutagenesis-validated functional residues (13):

Position	Phenotype
85	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
92	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
150	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
205	inhibits dipeptidyl peptidase activity.
206	inhibits dipeptidyl peptidase activity.
219	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
229	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
281	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
321	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
520	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
685	does not inhibit dipeptidyl peptidase activity, interaction with ada and homodimer formation.
750	inhibits weakly homodimerization and dipeptidyl peptidase activity.
750	inhibits strongly homodimerization, dipeptidyl peptidase activity, interaction with card11 and t-cell costimulation acti

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381771	Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-400511	Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)

MSigDB gene sets: 432 (showing top): MODULE_172, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_BEHAVIOR, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOCC_VACUOLAR_MEMBRANE, GOBP_MEMBRANE_FUSION, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION

GO Biological Process (20): behavioral fear response (GO:0001662), response to hypoxia (GO:0001666), proteolysis (GO:0006508), cell adhesion (GO:0007155), positive regulation of cell population proliferation (GO:0008284), negative regulation of extracellular matrix disassembly (GO:0010716), peptide hormone processing (GO:0016486), receptor-mediated endocytosis of virus by host cell (GO:0019065), T cell costimulation (GO:0031295), regulation of cell-cell adhesion mediated by integrin (GO:0033632), locomotory exploration behavior (GO:0035641), psychomotor behavior (GO:0036343), T cell activation (GO:0042110), endothelial cell migration (GO:0043542), symbiont entry into host cell (GO:0046718), receptor-mediated virion attachment to host cell (GO:0046813), membrane fusion (GO:0061025), negative regulation of neutrophil chemotaxis (GO:0090024), glucagon processing (GO:0120116), negative chemotaxis (GO:0050919)

GO Molecular Function (13): virus receptor activity (GO:0001618), protease binding (GO:0002020), aminopeptidase activity (GO:0004177), serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), chemorepellent activity (GO:0045499), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (15): extracellular region (GO:0005576), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), lamellipodium (GO:0030027), endocytic vesicle (GO:0030139), lamellipodium membrane (GO:0031258), membrane raft (GO:0045121), intercellular canaliculus (GO:0046581), extracellular exosome (GO:0070062), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Incretin synthesis, secretion, and inactivation	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
symbiont entry into host cell	2
exopeptidase activity	2
protein binding	2
behavioral defense response	1
fear response	1
response to stress	1
response to decreased oxygen levels	1
protein metabolic process	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of extracellular matrix disassembly	1
extracellular matrix disassembly	1
negative regulation of extracellular matrix organization	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
receptor-mediated endocytosis	1
endocytosis involved in viral entry into host cell	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
regulation of cell-cell adhesion	1
regulation of cell adhesion mediated by integrin	1
cell-cell adhesion mediated by integrin	1
locomotory behavior	1
exploration behavior	1
motor behavior	1
lymphocyte activation	1
cell migration	1
viral life cycle	1
symbiont entry into host	1
signaling receptor binding	1
virion attachment to host cell	1
membrane organization	1
neutrophil chemotaxis	1
negative regulation of granulocyte chemotaxis	1
regulation of neutrophil chemotaxis	1
negative regulation of neutrophil migration	1
peptide hormone processing	1

Protein interactions and networks

STRING

3386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPP4	ADA	P00813	997
DPP4	ACE2	Q9BYF1	995
DPP4	CAV1	Q03135	991
DPP4	PTPRC	P08575	987
DPP4	CXCR4	P30991	985
DPP4	FN1	P02751	983
DPP4	ITGB1	P05556	967
DPP4	GLP1R	P43220	965
DPP4	GCG	P01275	947
DPP4	IGF2R	P11717	945
DPP4	PREP	P48147	940
DPP4	GIP	P09681	926
DPP4	ANPEP	P15144	921
DPP4	BSG	P35613	914
DPP4	SLC5A2	P31639	909

IntAct

77 interactions, top by confidence:

A	B	Type	Score
DPP4	S	psi-mi:“MI:0915”(physical association)	0.840
DPP4	S	psi-mi:“MI:0403”(colocalization)	0.840
DPP4	S	psi-mi:“MI:0407”(direct interaction)	0.840
S	DPP4	psi-mi:“MI:0407”(direct interaction)	0.840
S	DPP4	psi-mi:“MI:0915”(physical association)	0.740
S	DPP4	psi-mi:“MI:0407”(direct interaction)	0.740
DPP4	CXCL10	psi-mi:“MI:0407”(direct interaction)	0.620
CXCL11	DPP4	psi-mi:“MI:0407”(direct interaction)	0.620
DPP4	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.620
CXCL9	DPP4	psi-mi:“MI:0407”(direct interaction)	0.620
DPP4	CCL11	psi-mi:“MI:0407”(direct interaction)	0.620
CCL11	DPP4	psi-mi:“MI:0194”(cleavage reaction)	0.620
DPP4	CXCL2	psi-mi:“MI:0194”(cleavage reaction)	0.620
CXCL9	DPP4	psi-mi:“MI:0194”(cleavage reaction)	0.620
DPP4	CXCL10	psi-mi:“MI:0194”(cleavage reaction)	0.620
DPP4	CXCL11	psi-mi:“MI:0194”(cleavage reaction)	0.620
DPP4	DPP4	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (613): DPP4 (Affinity Capture-MS), DPP4 (Affinity Capture-Western), FAP (Affinity Capture-Western), ADA (Affinity Capture-Western), DPP4 (Affinity Capture-MS), USP22 (Affinity Capture-Western), DPP4 (Reconstituted Complex), DPP4 (Affinity Capture-MS), DPP4 (Co-crystal Structure), S (Co-crystal Structure), DPP4 (Affinity Capture-Western), DPP4 (Proximity Label-MS), S (Reconstituted Complex), DPP4 (Affinity Capture-MS), CCL22 (Biochemical Activity)

ESM2 similar proteins: A0A0C1E1D0, A0A1L9WUM2, A0A1Q3EPF5, A0A4S8L6U5, A0S5V9, A1CHP1, A1CX29, A5D7B7, A7UKV8, B0Y6C5, B1A4F7, B2D0J4, B6V868, B8N970, C5FJE3, C9K7B8, D4APE2, D4CZ59, E2JFG1, E2JFG2, H2E7Q7, H2E7Q8, O14073, P0DRB8, P14740, P22411, P27487, P28843, P42658, P46101, P78875, P81425, P97321, P9WEN5, Q09541, Q12884, Q2UH35, Q4WAZ0, Q4WPH9, Q5AV79

Diamond homologs: A0S5V9, A1CHP1, A1CJQ1, A1CX29, A1D7R6, A2QEK7, A4QYQ5, A5D7B7, A6RBI0, A6SL49, A7EQZ1, A7UKV8, B0XYK8, B0Y6C5, B1A4F7, B2A951, B2D0J4, B2WC36, B6HFS8, B6QVW4, B6V868, B8MTH6, B8N076, B8N970, C0NUQ8, C0S7H1, C1FZL3, C1GT79, C4JHY5, C5FJE3, C5FYZ3, C5GVF3, C5JC30, C5P334, C6HRC7, C7YYG9, C9SJ15, D1Z9B4, D4APE2, D4AQT0

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GPC3	down-regulates	DPP4	binding
“Sitagliptin phosphate monohydrate”	down-regulates	DPP4	“chemical inhibition”
linagliptin	“down-regulates activity”	DPP4	“chemical inhibition”
vildagliptin	“down-regulates activity”	DPP4	“chemical inhibition”
saxagliptin	“down-regulates activity”	DPP4	“chemical inhibition”
sitagliptin	“down-regulates activity”	DPP4	“chemical inhibition”
alogliptin	“down-regulates activity”	DPP4	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Glucagon-type ligand receptors	5	59.7×	9e-07
Chemokine receptors bind chemokines	8	51.6×	3e-10
Peptide ligand-binding receptors	6	15.3×	8e-05
G alpha (i) signalling events	10	13.4×	1e-07
Signaling by Interleukins	6	13.3×	1e-04
G alpha (s) signalling events	5	12.6×	9e-04
GPCR ligand binding	5	11.1×	1e-03
Cytokine Signaling in Immune system	6	8.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	7	68.7×	3e-09
chemotaxis	8	33.0×	2e-08
adenylate cyclase-activating G protein-coupled receptor signaling pathway	8	27.4×	6e-08
neuropeptide signaling pathway	5	26.1×	1e-04
cell-cell signaling	8	16.9×	2e-06
positive regulation of cell migration	5	9.3×	4e-03
inflammatory response	8	9.1×	1e-04
G protein-coupled receptor signaling pathway	7	7.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

150 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	97
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
253674	GRCh37/hg19 2q24.2-24.3(chr2:161542325-164640864)x1	Pathogenic
523687	Single allele	Likely pathogenic
932936	GRCh37/hg19 2q24.2(chr2:161561653-163178787)	Likely pathogenic

SpliceAI

3413 predictions. Top by Δscore:

Variant	Effect	Δscore
2:161995371:TT:T	acceptor_gain	1.0000
2:161995373:C:CC	acceptor_gain	1.0000
2:161995373:C:G	acceptor_loss	1.0000
2:161995374:T:C	acceptor_loss	1.0000
2:162005743:A:AC	donor_gain	1.0000
2:162005744:C:CC	donor_gain	1.0000
2:162005744:CT:C	donor_gain	1.0000
2:162016762:A:C	donor_gain	1.0000
2:162016762:ACTT:A	donor_loss	1.0000
2:162016763:CTT:C	donor_loss	1.0000
2:162016764:TTACT:T	donor_loss	1.0000
2:162016765:TA:T	donor_loss	1.0000
2:162016766:A:AC	donor_gain	1.0000
2:162016766:ACTTG:A	donor_loss	1.0000
2:162016767:C:CA	donor_gain	1.0000
2:162016767:C:G	donor_loss	1.0000
2:162016767:CT:C	donor_gain	1.0000
2:162016767:CTT:C	donor_gain	1.0000
2:162016767:CTTG:C	donor_gain	1.0000
2:162016767:CTTGT:C	donor_gain	1.0000
2:162016862:CAGCC:C	acceptor_gain	1.0000
2:162016863:AGCC:A	acceptor_gain	1.0000
2:162016864:GCC:G	acceptor_gain	1.0000
2:162016865:CC:C	acceptor_gain	1.0000
2:162016865:CCC:C	acceptor_gain	1.0000
2:162016865:CCCTA:C	acceptor_loss	1.0000
2:162016866:CC:C	acceptor_gain	1.0000
2:162016867:C:CA	acceptor_loss	1.0000
2:162016867:C:CC	acceptor_gain	1.0000
2:162016867:C:T	acceptor_gain	1.0000

AlphaMissense

5060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:161995303:C:G	D708H	0.999
2:161993364:A:C	H740Q	0.998
2:161993364:A:T	H740Q	0.998
2:161995302:T:A	D708V	0.998
2:161995323:A:G	L701P	0.998
2:162005791:C:G	R669P	0.998
2:162008574:A:G	W659R	0.998
2:162008574:A:T	W659R	0.998
2:162038312:C:A	W201C	0.998
2:162038312:C:G	W201C	0.998
2:162038314:A:G	W201R	0.998
2:162038314:A:T	W201R	0.998
2:161995010:G:T	A717D	0.997
2:161995303:C:A	D708Y	0.997
2:161995311:C:T	G705E	0.997
2:162008572:C:A	W659C	0.997
2:162008572:C:G	W659C	0.997
2:162008594:G:T	A652D	0.997
2:162008595:C:G	A652P	0.997
2:162008661:A:G	S630P	0.997
2:162047410:C:A	W62C	0.997
2:162047410:C:G	W62C	0.997
2:162047412:A:G	W62R	0.997
2:162047412:A:T	W62R	0.997
2:161993366:G:C	H740D	0.996
2:161993384:A:G	W734R	0.996
2:161993384:A:T	W734R	0.996
2:161995011:C:G	A717P	0.996
2:161995301:A:C	D708E	0.996
2:161995301:A:T	D708E	0.996

dbSNP variants (sampled 300 via entrez): RS1000013870 (2:162068689 T>A,C), RS1000038446 (2:162071008 T>C), RS1000053373 (2:162022906 G>A,T), RS1000063989 (2:162031449 GC>G), RS1000085499 (2:162068430 C>G), RS1000093113 (2:162040624 A>G), RS1000128448 (2:162029246 C>A), RS1000140430 (2:162021913 A>G), RS1000158547 (2:162055775 C>CTTTG), RS1000165910 (2:162045123 C>T), RS1000237043 (2:162064993 C>T), RS1000253919 (2:162047953 C>T), RS1000298157 (2:162009357 G>A,C), RS1000306177 (2:162047700 A>G), RS1000315290 (2:162018777 A>G)

Disease associations

OMIM: gene MIM:102720 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (1): Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST001485_1	Hippocampal volume	3.000000e-07
GCST002433_3	Rheumatoid arthritis	2.000000e-21
GCST002433_6	Rheumatoid arthritis	1.000000e-08
GCST002539_38	Schizophrenia	5.000000e-08
GCST004267_2	Blood osmolality (transformed sodium)	7.000000e-08
GCST005141_2	Cognitive ability (MTAG)	9.000000e-11
GCST005142_27	Cognitive ability	6.000000e-06
GCST005316_162	Intelligence (MTAG)	6.000000e-13
GCST005316_164	Intelligence (MTAG)	1.000000e-08
GCST005316_166	Intelligence (MTAG)	9.000000e-09
GCST006268_500	Reaction time	5.000000e-09
GCST006269_1215	General cognitive ability	4.000000e-08
GCST006269_610	General cognitive ability	5.000000e-13
GCST006803_53	Schizophrenia	4.000000e-07
GCST006870_1	Hippocampal tail volume	9.000000e-22
GCST006871_7	Total hippocampal volume	5.000000e-13
GCST006881_1	Hippocampal tail volume (corrected for total hippocampal volume)	3.000000e-13
GCST006886_2	Subiculum volume	6.000000e-11
GCST006891_1	Dentate gyrus molecular layer volume	2.000000e-10
GCST006921_12	Regular attendance at a pub or social club	2.000000e-08
GCST007277_3	Tourette syndrome	2.000000e-07
GCST007327_214	Smoking status (ever vs never smokers)	2.000000e-15
GCST008810_56	Smoking initiation (ever regular vs never regular)	2.000000e-12
GCST009597_166	Multiple sclerosis	2.000000e-07
GCST010042_115	Asthma	1.000000e-08
GCST010043_100	Asthma	2.000000e-09
GCST010698_37	Subcortical volume (min-P)	9.000000e-30
GCST010699_113	Brain morphology (min-P)	5.000000e-08
GCST010700_43	Cortical thickness (MOSTest)	4.000000e-08
GCST010701_88	Cortical surface area (MOSTest)	1.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0008393	reaction time measurement
EFO:0009592	social interaction measurement
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111469 (SELECTIVITY GROUP), CHEMBL284 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

33 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 362,880 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1090	VIDARABINE	4	7,461
CHEMBL1201174	SITAGLIPTIN PHOSPHATE	4	256
CHEMBL1422	SITAGLIPTIN	4	26,582
CHEMBL142703	VILDAGLIPTIN	4	20,312
CHEMBL1431	METFORMIN	4	167,749
CHEMBL1650443	TRELAGLIPTIN	4	1,367
CHEMBL1779710	EVOGLIPTIN	4	762
CHEMBL1929396	ANAGLIPTIN	4	1,091
CHEMBL2105754	TRELAGLIPTIN SUCCINATE	4	155
CHEMBL2105762	OMARIGLIPTIN	4	1,107
CHEMBL2147777	TENELIGLIPTIN	4	1,406
CHEMBL237500	LINAGLIPTIN	4	5,282
CHEMBL376359	ALOGLIPTIN	4	3,750
CHEMBL385517	SAXAGLIPTIN ANHYDROUS	4	18,553
CHEMBL430	GEMIFLOXACIN	4	9,759
CHEMBL515387	GOSOGLIPTIN	4	785
CHEMBL1082462	DBPR-108	3	47
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL165	RESVERATROL	3	60,144
CHEMBL2103745	SAXAGLIPTIN	3	7
CHEMBL297453	EPIGALOCATECHIN GALLATE	3
CHEMBL4296719	DUTOGLIPTIN	3
CHEMBL4297435	RETAGLIPTIN	3
CHEMBL50	QUERCETIN	3
CHEMBL67279	TALABOSTAT	3
CHEMBL151	LUTEOLIN	2
CHEMBL275638	FLAVONE	2
CHEMBL288114	GALLIC ACID	2
CHEMBL44	GENISTEIN	2
CHEMBL4646510	COFROGLIPTIN	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17574	DPP4		0.00	0
rs13015258	DPP4		0.00	0
rs17848916	DPP4		0.00	0
rs2909451	DPP4		0.00	0
rs759717	DPP4		0.00	0
rs4664443	DPP4		0.00	0
rs2970932	DPP4		0.00	0
rs2268889	DPP4		0.00	0
rs1861975	DPP4		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S9: Prolyl oligopeptidase

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
begelomab	Binding	10.0	pKd
talabostat	Inhibition	9.74	pKi
teneligliptin	Inhibition	9.43	pIC50
saxagliptin	Inhibition	9.2	pKi
omarigliptin	Inhibition	9.1	pKi
linagliptin	Inhibition	9.0	pKi
compound 24dd [PMID: 20684603]	Inhibition	8.85	pKi
fotagliptin	Inhibition	8.66	pIC50
alogliptin	Inhibition	8.5	pIC50
anagliptin	Inhibition	8.42	pIC50
cofrogliptin	Inhibition	8.38	pIC50
prusogliptin	Inhibition	8.3	pIC50
ZY15557	Competitive	8.26	pKi
sitagliptin	Inhibition	8.1	pIC50
vildagliptin	Inhibition	8.0	pIC50
cetagliptin	Inhibition	7.77	pIC50
compound 1 [Xiao et al. 2014]	Inhibition	6.6	pIC50
compound 9 [PMID: 20718420]	Inhibition	4.7	pIC50

Binding affinities (BindingDB)

989 measured of 1194 human assays (1197 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-[(3R)-3-aminopiperidin-1-ium-1-ylidene]-7-but-2-ynyl-1-[(5-fluoro-1,3-benzothiazol-2-yl)methyl]-3-methyl-5H-purine-2,6-dione	IC50	0.05 nM	US-9255098: Xanthine derivative
3-[[8-[(3R)-3-aminopiperidin-1-ium-1-ylidene]-7-but-2-ynyl-3-methyl-2,6-dioxo-5H-purin-1-yl]methyl]pyrazine-2-carbonitrile	IC50	0.08 nM	US-10358449: Xanthine derivative
5-(aminomethyl)-6-(2,4-dichlorophenyl)-2-(3,5-dimethoxyphenyl)pyrimidin-4-amine	IC50	0.1 nM
8-[(3R)-3-aminopiperidin-1-ium-1-ylidene]-1-(1,3-benzothiazol-2-ylmethyl)-7-but-2-ynyl-3-methyl-5H-purine-2,6-dione	IC50	0.1 nM	US-9255098: Xanthine derivative
5-[(3R,5S)-5-amino-6-(2,5-difluorophenyl)thian-3-yl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazole-3-carboxamide	IC50	0.17 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
1c-meta-F	IC50	0.2 nM
1c-para-F	IC50	0.2 nM
8-[(3R)-3-aminopiperidin-1-ium-1-ylidene]-7-but-2-ynyl-1-[(5-chloro-1,3-benzothiazol-2-yl)methyl]-3-methyl-5H-purine-2,6-dione	IC50	0.2 nM	US-9255098: Xanthine derivative
2-[[8-[(3R)-3-aminopiperidin-1-ium-1-ylidene]-7-but-2-ynyl-3-methyl-2,6-dioxo-5H-purin-1-yl]methyl]-6-fluorobenzonitrile	IC50	0.21 nM	US-10358449: Xanthine derivative
(R)-1-((S)-2-aminopropanoyl)pyrrolidin-2-ylboronic acid	IC50	0.26 nM	US-8933056: Soft protease inhibitors and pro-soft forms thereof
(R)-8-(3-aminopiperidin-1-yl)-7-(but-2-ynyl)-3-methyl-1-((4-methylquinazolin-2-yl)methyl)-1H-purine-2,6(3H,7H)-dione	IC50	0.32 nM
[(2R)-1-[(2S)-2-aminopropanethioyl]pyrrolidin-2-yl]boronic acid	IC50	0.35 nM	US-8933056: Soft protease inhibitors and pro-soft forms thereof
2-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-5-[(4-methylquinazolin-2-yl)methyl]-7,8-dihydroimidazo[2,1-b]purin-4-one	IC50	0.38 nM	US-8691832
(3S,5R)-2-(2,5-difluorophenyl)-1-[(2S)-2-fluoropropyl]-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)piperidin-3-amine	IC50	0.4 nM	US-8716482: Substituted aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(2S)-1-{[(2S,5R)-5-{[(6-bromo-2H-1,3-benzodioxol-5-yl)oxy]methyl}pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.41 nM
5-chloro-6-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}pyridine-3-carboxylic acid	KI	0.45 nM
5-[(3R,5S)-5-amino-6-(2,5-difluorophenyl)thian-3-yl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazole-3-carbonitrile	IC50	0.46 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(3S,5R)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-2-(2,3,5-trifluorophenyl)thian-3-amine	IC50	0.5 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(2R,3S,5R)-2-(2,5-difluorophenyl)-5-[3-methyl-2-(1-methylcyclopropyl)sulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl]oxepan-3-amine	IC50	0.5 nM	US-8980929: Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes
(2S)-1-{[(2S,5R)-5-(2-chloro-4-cyanophenoxymethyl)pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.6 nM
(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile; 2,2,2-trifluoroacetic acid	KI	0.6 nM
(3S,5R)-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)thian-3-amine	IC50	0.6 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(2S)-1-{[(2S,5R)-5-(2,4-dichloro-5-nitrophenoxymethyl)pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.63 nM
3-bromo-4-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}benzoic acid	KI	0.66 nM
N-(4-chloro-3-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}phenyl)-1H-pyrazole-3-carboxamide	KI	0.66 nM
6-chloro-5-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}pyridine-3-carboxylic acid	KI	0.68 nM
(2S)-1-{[(2S,5R)-5-(2-bromo-4-methanesulfonylphenoxymethyl)pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.68 nM
(3S,5R)-5-(2-cyclopropylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidin-3-amine	IC50	0.7 nM	US-8716482: Substituted aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(3S,5R)-2-(2,5-difluorophenyl)-5-[2-(trifluoromethyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]thian-3-amine	IC50	0.7 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(3S,5R)-2-(2,5-difluorophenyl)-5-(2-phenyl-4,6-dihydro-1H-pyrrolo[3,4-d]imidazol-5-yl)thian-3-amine	IC50	0.7 nM	US-8853212: Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
(+)-Ethyl 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylate	IC50	0.7 nM
(2S)-1-{[(2S,5R)-5-{[(2-chloropyridin-3-yl)oxy]methyl}pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.72 nM
N-(3-bromo-4-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}phenyl)benzenesulfonamide	KI	0.73 nM
6-Iodo-N3-(3-nitrobenzylidene)-2-phenyl-N4-(thiazol-2-yl)-quinazoline-3,4-(4H)-diamine (7g)	IC50	0.76 nM
4-chloro-3-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}benzoic acid	KI	0.82 nM
(2S)-1-{[(2S,5R)-5-(2-chlorophenoxymethyl)pyrrolidin-2-yl]carbonyl}pyrrolidine-2-carbonitrile	KI	0.85 nM
BMS-477118 analogue	KI	0.9 nM
1c-meta-Me	IC50	0.9 nM
(3S,5R)-1-methyl-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidin-3-amine	IC50	0.9 nM	US-8716482: Substituted aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
3-chloro-4-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}benzoic acid	KI	0.93 nM
(3S,5R)-5-(2-cyclopropylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-2-(2,5-difluorophenyl)oxan-3-amine	IC50	1 nM	US-8592371: Aminotetrahydropyrans as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
4-bromo-3-{[(2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl]methoxy}benzoic acid	KI	1 nM
(2S)-1-[(2S)-2-amino-2-cyclopentylacetyl]pyrrolidine-2-carbonitrile	KI	1 nM
(7S)-2-[(3R)-3-aminopiperidin-1-yl]-3-but-2-ynyl-7-methyl-5-[(4-methylquinazolin-2-yl)methyl]-7,8-dihydroimidazo[2,1-b]purin-4-one	IC50	1 nM	US-8691832
2-[(3S,5R)-3-amino-2-(2,5-difluorophenyl)-5-(4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-5-yl)piperidin-1-yl]-1-[(3R)-3-fluoropyrrolidin-1-yl]ethanone	IC50	1 nM	US-8716482: Substituted aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
2-[4-{{2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid	KI	1 nM
[(2R)-1-[(2S)-2-amino-2-cyclohexylacetyl]pyrrolidin-2-yl]boronic acid	IC50	1 nM	US-8933056: Soft protease inhibitors and pro-soft forms thereof
8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-(quinazolin-2-ylmethyl)-4,5-dihydropurine-2,6-dione	IC50	1 nM	US-9321791: 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylisoquinolin-1-yl)methyl]-4,5-dihydropurine-2,6-dione	IC50	1 nM	US-9321791: 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
2-[2-[2-[8-[(3R)-3-aminopiperidin-1-yl]-7-[(E)-but-2-enyl]-3-methyl-2,6-dioxo-4,5-dihydropurin-1-yl]acetyl]phenoxy]-N-methylacetamide	IC50	1 nM	US-9321791: 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions

ChEMBL bioactivities

5078 potent at pChembl≥5 of 5391 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL63860
10.30	IC50	0.05	nM	CHEMBL4113723
10.10	IC50	0.08	nM	CHEMBL4113723
10.10	IC50	0.08	nM	CHEMBL5914058
10.09	Ki	0.082	nM	CHEMBL98869
10.05	IC50	0.09	nM	CHEMBL5269668
10.00	IC50	0.1	nM	CHEMBL34062
10.00	IC50	0.1	nM	CHEMBL186877
10.00	IC50	0.1	nM	LINAGLIPTIN
10.00	IC50	0.1	nM	CHEMBL4111229
10.00	IC50	0.1	nM	CHEMBL4448186
10.00	IC50	0.1	nM	TALABOSTAT
9.92	IC50	0.12	nM	CHEMBL3806052
9.89	IC50	0.13	nM	CHEMBL370046
9.89	IC50	0.13	nM	CHEMBL194717
9.89	IC50	0.13	nM	CHEMBL5220657
9.89	IC50	0.13	nM	CHEMBL456420
9.85	IC50	0.14	nM	CHEMBL3805966
9.85	IC50	0.14	nM	CHEMBL5220613
9.85	IC50	0.14	nM	LINAGLIPTIN
9.82	IC50	0.15	nM	CHEMBL4111229
9.82	IC50	0.15	nM	CHEMBL445437
9.80	IC50	0.16	nM	CHEMBL5220594
9.77	IC50	0.17	nM	CHEMBL3644459
9.75	Kd	0.177	nM	CHEMBL4550812
9.74	IC50	0.18	nM	CHEMBL370540
9.74	Ki	0.18	nM	TALABOSTAT
9.74	IC50	0.18	nM	CHEMBL4465482
9.74	IC50	0.18	nM	CHEMBL1203953
9.74	IC50	0.18	nM	CHEMBL5951803
9.72	IC50	0.19	nM	CHEMBL371143
9.70	IC50	0.2	nM	CHEMBL2147704
9.70	IC50	0.2	nM	CHEMBL4109453
9.70	Ki	0.2	nM	CHEMBL1215018
9.70	IC50	0.2	nM	CHEMBL34842
9.70	IC50	0.2	nM	CHEMBL36666
9.68	IC50	0.21	nM	CHEMBL402163
9.68	IC50	0.21	nM	CHEMBL6057823
9.68	IC50	0.21	nM	LINAGLIPTIN
9.68	IC50	0.21	nM	CHEMBL5870057
9.66	IC50	0.22	nM	CHEMBL4461587
9.66	IC50	0.22	nM	CHEMBL5434074
9.64	IC50	0.23	nM	CHEMBL3805629
9.62	IC50	0.24	nM	CHEMBL3806041
9.60	IC50	0.25	nM	CHEMBL195420
9.59	IC50	0.26	nM	CHEMBL2147703
9.59	IC50	0.26	nM	CHEMBL63860
9.59	IC50	0.26	nM	CHEMBL5219939
9.59	Ki	0.26	nM	CHEMBL1910126
9.57	Ki	0.27	nM	CHEMBL380350

PubChem BioAssay actives

4087 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Linagliptin	1631907: Binding affinity to human recombinant DPP4 (39 to 766 residues) by surface plasmon resonance analysis	kd	<0.0001	uM
[(2R)-1-[(2S)-2-aminopropanoyl]pyrrolidin-2-yl]boronic acid	287007: Inhibition of human placental DPP4	ki	<0.0001	uM
(2S,3S)-3-amino-2-[4-(4-fluorophenyl)phenyl]-4-[(3S)-3-fluoropyrrolidin-1-yl]-N,N-dimethyl-4-oxobutanamide	393688: Inhibition of DPP4	ic50	<0.0001	uM
4-[[(3S,5S)-5-[(2S)-2-cyanopyrrolidine-1-carbonyl]pyrrolidin-3-yl]amino]benzene-1,2-dicarbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0001	uM
(2S)-2-amino-4-[(4-chlorophenyl)methylamino]-1-piperidin-1-ylbutan-1-one	270814: Inhibition of DPP4	ki	0.0001	uM
2-[[8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]-5-chlorobenzoic acid	1570155: Inhibition of recombinant human DPP4 expressed in baculovirus infected Sf9 insect cells using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition measured at 60 secs interval for 20 mins by fluorometic method	ic50	0.0001	uM
[(E)-3-ethoxy-3-oxoprop-1-enyl] (2S)-1-[(2S)-2,6-bis[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0001	uM
ethenyl (2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0001	uM
3-[[8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-1-[(2-cyano-3-pyridinyl)methyl]-2,6-dioxo-4,5-dihydropurin-3-yl]methyl]pyridine-2-carbonitrile	1941040: Inhibition of DPP4 (unknown origin) using Gly-Pro-7-amido-4-methylcoumarin as substrate incubated for 30 mins by fluorescence analysis	ic50	0.0001	uM
(2R,3S,5R)-2-(2,5-difluorophenyl)-5-(4,7,8,9,12-pentazatricyclo[6.4.0.02,6]dodeca-1,6,9,11-tetraen-4-yl)oxan-3-amine	1301045: Inhibition of human DPP4	ic50	0.0001	uM
6-(2,4-dichlorophenyl)-2-(3,5-dimethoxyphenyl)-5-[(dimethylamino)methyl]-N,N-dimethylpyrimidin-4-amine	240872: Inhibitory concentration against Dipeptidyl peptidase IV	ic50	0.0001	uM
4-[[(3S)-5-[(2S)-2-cyanopyrrolidine-1-carbonyl]pyrrolidin-3-yl]amino]benzene-1,2-dicarbonitrile	393692: Inhibition of human DPP4	ic50	0.0001	uM
(2S)-1-[(4S)-4-(3-chloro-4-cyanoanilino)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	393692: Inhibition of human DPP4	ic50	0.0001	uM
5-(aminomethyl)-6-(2,4-dichlorophenyl)-2-(3,5-dimethoxyphenyl)pyrimidin-4-amine	1796753: Fluorogenic Assay from Article 10.1016/j.bmcl.2004.01.019: “Aminomethylpyrimidines as novel DPP-IV inhibitors: a 10(5)-fold activity increase by optimization of aromatic substituents.”	ic50	0.0001	uM
(2S)-1-[(2S,4S)-4-(4-nitroanilino)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0002	uM
5-(aminomethyl)-6-(2,4-dichlorophenyl)-2-(4-fluorophenyl)pyrimidin-4-amine	1796753: Fluorogenic Assay from Article 10.1016/j.bmcl.2004.01.019: “Aminomethylpyrimidines as novel DPP-IV inhibitors: a 10(5)-fold activity increase by optimization of aromatic substituents.”	ic50	0.0002	uM
5-(aminomethyl)-6-(2,4-dichlorophenyl)-2-(3-fluorophenyl)pyrimidin-4-amine	1796753: Fluorogenic Assay from Article 10.1016/j.bmcl.2004.01.019: “Aminomethylpyrimidines as novel DPP-IV inhibitors: a 10(5)-fold activity increase by optimization of aromatic substituents.”	ic50	0.0002	uM
(1S,2R,5S)-5-(11-methyl-1,4,8,10,12-pentazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-4-yl)-2-(2,4,5-trifluorophenyl)cyclohexan-1-amine	1301045: Inhibition of human DPP4	ic50	0.0002	uM
(1S,2R,5S)-5-(12-cyclopropyl-1,4,8,10,11-pentazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-4-yl)-2-(2,4,5-trifluorophenyl)cyclohexan-1-amine	1301045: Inhibition of human DPP4	ic50	0.0002	uM
(2S,3R)-2-amino-9-methoxy-3-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-benzo[f]chromene-8-carbonitrile	1638343: Binding affinity to DPP4 (unknown origin) expressed in baculovirus expressing system	kd	0.0002	uM
2-[[8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]-5-bromobenzoic acid	1570155: Inhibition of recombinant human DPP4 expressed in baculovirus infected Sf9 insect cells using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition measured at 60 secs interval for 20 mins by fluorometic method	ic50	0.0002	uM
2-[[8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]-4-chlorobenzoic acid	1570155: Inhibition of recombinant human DPP4 expressed in baculovirus infected Sf9 insect cells using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition measured at 60 secs interval for 20 mins by fluorometic method	ic50	0.0002	uM
ethenyl (2S)-1-[(2S)-2,6-bis[(2-methylpropan-2-yl)oxycarbonylamino]hexanoyl]pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0002	uM
2-[[2-[(3R)-3-aminopiperidin-1-yl]-4-oxo-6-pyridin-3-ylthieno[3,2-d]pyrimidin-3-yl]methyl]-4-fluorobenzonitrile	2013183: Inhibition of DPP-4 (unknown origin) using Gly-Pro-AMC as substrate preincubated for 10 mins followed by substrate addition measured after 20 mins by fluorescence based assay	ic50	0.0002	uM
(3R)-3-amino-1-[(8R)-8-[(4-fluorophenyl)methyl]-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;hydrochloride	312998: Inhibition of DPP4	ic50	0.0002	uM
(2S)-1-[(2S,4S)-4-(4-cyanoanilino)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0002	uM
N-[(3S)-1-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carbonyl]pyrrolidin-3-yl]methanesulfonamide	499232: Inhibition of human recombinant DPP4 assessed as Gly-Pro-pNA cleavage	ki	0.0002	uM
(2S,3S)-3-[3-(2-chloro-4-methylsulfonylphenyl)-1,2,4-oxadiazol-5-yl]-1-cyclopentylidene-4-cyclopropyl-1-fluorobutan-2-amine;2,2,2-trifluoroacetic acid	322052: Inhibition of human recombinant DPP4 expressed in insect cell	ic50	0.0002	uM
[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid	254910: Inhibitory concentration against human dipeptidylpeptidase 4	ic50	0.0003	uM
saxagliptin anhydrous	1631907: Binding affinity to human recombinant DPP4 (39 to 766 residues) by surface plasmon resonance analysis	kd	0.0003	uM
(2S)-1-[(2S,5R)-5-[(2,4-dichloro-5-nitrophenoxy)methyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	266034: Inhibition of human recombinant DPP4 by tight-binding assay	ki	0.0003	uM
N-[4-chloro-3-[[(2R,5S)-5-[(2S)-2-cyanopyrrolidine-1-carbonyl]pyrrolidin-2-yl]methoxy]phenyl]-1H-pyrazole-5-carboxamide	266034: Inhibition of human recombinant DPP4 by tight-binding assay	ki	0.0003	uM
N-[5-[(3R,5S,6R)-5-amino-6-(2,5-difluorophenyl)oxan-3-yl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-1H-imidazole-5-sulfonamide	1262431: Inhibition of recombinant human DPP4 expressed in Sf9 cells using Gly-Pro-AMC substrate after 30 mins by plate reader analysis	ic50	0.0003	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylacetamide	778687: Inhibition of human DPP4 assessed as Gly-Pro-pNA cleavage preincubated for 40 mins followed by substrate addition	ki	0.0003	uM
[(E)-2-phenylethenyl] (2S)-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0003	uM
ethenyl (2S)-1-(2-aminoacetyl)pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0003	uM
[(E)-2-phenylethenyl] (2S)-1-(2-aminoacetyl)pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0003	uM
[(E)-2-phenylethenyl] (2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carboxylate	1917937: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay	ic50	0.0003	uM
(2S)-2-[4-[[[(4R)-3-[(3R)-3-amino-4-(2,5-difluorophenyl)butanoyl]-1,3-thiazolidine-4-carbonyl]amino]methyl]anilino]-3-methylbutanoic acid	1926211: Inhibition of DPP4 (unknown origin)	ic50	0.0003	uM
(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(pyrazol-1-ylmethyl)-1,4-diazepan-2-one	1797040: Dipeptidyl Peptidase Inhibition Assay from Article 10.1016/j.bmcl.2006.09.099: “(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.”	ic50	0.0003	uM
6-[[(3S,5S)-5-[(2S)-2-cyanopyrrolidine-1-carbonyl]pyrrolidin-3-yl]amino]pyridine-3-carbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0003	uM
(2S)-1-[(2S,4S)-4-(4-methoxyanilino)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0003	uM
(2S)-1-[(2S,4S)-4-(3,4-dimethoxyanilino)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile	241057: Inhibitory concentration against human dipeptidylpeptidase IV	ic50	0.0003	uM
(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(pyrazin-2-ylmethyl)-1,4-diazepan-2-one	273979: In vitro inhibition of human DPP-4 activity	ic50	0.0003	uM
(3R)-3-amino-1-[3-(trifluoromethyl)-8-[[2-(trifluoromethyl)phenyl]methyl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;hydrochloride	312998: Inhibition of DPP4	ic50	0.0003	uM
(3R)-3-amino-1-[8-[(4-fluorophenyl)-hydroxymethyl]-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;hydrochloride	312998: Inhibition of DPP4	ic50	0.0003	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(2-methylsulfonylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499232: Inhibition of human recombinant DPP4 assessed as Gly-Pro-pNA cleavage	ki	0.0003	uM
2-[[2-[(3R)-3-aminopiperidin-1-yl]-4-oxothieno[3,2-d]pyrimidin-3-yl]methyl]benzonitrile	567004: Inhibition of DPP4 after 20 mins by fluorescence assay	ic50	0.0003	uM
(2S)-2-[4-[[[(4R)-3-[3-amino-4-(2,5-difluorophenyl)butanoyl]-1,3-thiazolidine-4-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid;2,2,2-trifluoroacetic acid	241218: Inhibition of human recombinant Dipeptidylpeptidase IV	ic50	0.0003	uM
[(2R)-1-(2-aminoacetyl)pyrrolidin-2-yl]boronic acid	390968: Inhibition of human placental DPP4	ki	0.0004	uM

CTD chemical–gene interactions

88 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	6
Sitagliptin Phosphate	affects binding, decreases activity	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Progesterone	affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
nickel sulfate	increases expression, decreases expression	2
entinostat	affects cotreatment, increases expression	2
saxagliptin	decreases activity	2
Arsenic Trioxide	decreases expression	2
Vildagliptin	decreases activity	2
Acetaminophen	decreases expression, increases expression	2
Allergens	affects cotreatment, decreases expression, decreases abundance, increases expression	2
Vehicle Emissions	affects cotreatment, decreases expression, decreases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Doxorubicin	decreases expression, increases cleavage, increases reaction, increases expression, increases response to substance	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Quercetin	affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Particulate Matter	decreases abundance, increases expression, decreases expression, affects cotreatment	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1

ChEMBL screening assays

635 unique, capped per target: 584 binding, 41 admet, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL665781	Binding	Selectivity index of compound was determined for human Dipeptidylpeptidase IV to that of Dipeptidyl-peptidase II	Design, synthesis, and SAR of potent and selective dipeptide-derived inhibitors for dipeptidyl peptidases. — J Med Chem
CHEMBL3089985	ADMET	Prodrug conversion assessed as dipeptidyl peptidase 4-mediated ACV formation in human serum at 50 uM after 1 hr by HPLC analysis	Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme. — Eur J Med Chem
CHEMBL4616458	Functional	Ex-vivo inhibition of DPP4 in plasma of T2D patient assessed as time duration during which DPP4 inhibition rate stays above 80% during phase 2 clinical study	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

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8EV	Abcam HCT 116 DPP4 KO	Cancer cell line	Male
CVCL_B9H3	Abcam A-549 DPP4 KO	Cancer cell line	Male
CVCL_D2EV	Abcam MCF-7 DPP4 KO	Cancer cell line	Female
CVCL_D8K8	Ubigene HCT 116 DPP4 KO	Cancer cell line	Male
CVCL_SL16	HAP1 DPP4 (-) 1	Cancer cell line	Male
CVCL_SL17	HAP1 DPP4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.