DPP8

Summary

DPP8 (dipeptidyl peptidase 8, HGNC:16490) is a protein-coding gene on chromosome 15q22.31, encoding Dipeptidyl peptidase 8 (Q6V1X1). Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase IV in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 54878 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 109 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_130434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16490
Approved symbol	DPP8
Name	dipeptidyl peptidase 8
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	DP8, DPRP1, MSTP141, FLJ14920, FLJ20283, MGC26191
Ensembl gene	ENSG00000074603
Ensembl biotype	protein_coding
OMIM	606819
Entrez	54878

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 47 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000300141, ENST00000321147, ENST00000341861, ENST00000358939, ENST00000395652, ENST00000558363, ENST00000558529, ENST00000558559, ENST00000558786, ENST00000559233, ENST00000559526, ENST00000560048, ENST00000560194, ENST00000560436, ENST00000560597, ENST00000560665, ENST00000872740, ENST00000872741, ENST00000872742, ENST00000872743, ENST00000872744, ENST00000872745, ENST00000872746, ENST00000872747, ENST00000872748, ENST00000872749, ENST00000872750, ENST00000872751, ENST00000872752, ENST00000872753, ENST00000872754, ENST00000872755, ENST00000872756, ENST00000872757, ENST00000872758, ENST00000872759, ENST00000872760, ENST00000872761, ENST00000945897, ENST00000945898, ENST00000945899, ENST00000945900, ENST00000945901, ENST00000945902, ENST00000945903, ENST00000945904, ENST00000945905, ENST00000945906, ENST00000945907, ENST00000945908, ENST00000945909, ENST00000945910

RefSeq mRNA: 6 — MANE Select: NM_130434 NM_001320875, NM_001320876, NM_017743, NM_130434, NM_197960, NM_197961

CCDS: CCDS10207, CCDS10208, CCDS10209, CCDS10210

Canonical transcript exons

ENST00000300141 — 20 exons

Exon	Start	End
ENSE00000885209	65463761	65463906
ENSE00001200707	65497864	65498032
ENSE00001281378	65507243	65507355
ENSE00001281424	65467071	65467223
ENSE00001281610	65485099	65485160
ENSE00001354040	65474209	65474288
ENSE00001354043	65478880	65479039
ENSE00001354044	65480222	65480399
ENSE00001354048	65481515	65481615
ENSE00001354077	65487690	65487818
ENSE00001354080	65490189	65490299
ENSE00001354084	65500606	65500779
ENSE00001854963	65442467	65447006
ENSE00001954107	65517486	65517689
ENSE00003458613	65454263	65454415
ENSE00003474738	65456225	65456371
ENSE00003491262	65450999	65451110
ENSE00003514344	65512295	65512564
ENSE00003532925	65451960	65452102
ENSE00003582233	65466678	65466813

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0227 / max 156.6170, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150555	19.2551	1808
150556	1.2643	902
150554	1.1084	687
150552	0.3604	141
150553	0.0346	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.50	gold quality
secondary oocyte	CL:0000655	97.98	gold quality
nipple	UBERON:0002030	96.76	gold quality
middle temporal gyrus	UBERON:0002771	96.75	gold quality
pons	UBERON:0000988	96.53	gold quality
postcentral gyrus	UBERON:0002581	96.45	gold quality
parietal lobe	UBERON:0001872	96.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.95	gold quality
biceps brachii	UBERON:0001507	95.60	gold quality
superior vestibular nucleus	UBERON:0007227	95.55	gold quality
palpebral conjunctiva	UBERON:0001812	95.48	gold quality
adult organism	UBERON:0007023	95.44	gold quality
jejunum	UBERON:0002115	95.35	gold quality
oocyte	CL:0000023	95.33	gold quality
medulla oblongata	UBERON:0001896	95.28	gold quality
pylorus	UBERON:0001166	95.14	gold quality
visceral pleura	UBERON:0002401	94.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.86	gold quality
superior surface of tongue	UBERON:0007371	94.86	gold quality
urethra	UBERON:0000057	94.85	gold quality
body of tongue	UBERON:0011876	94.84	gold quality
inferior vagus X ganglion	UBERON:0005363	94.83	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.82	gold quality
superior frontal gyrus	UBERON:0002661	94.81	gold quality
deltoid	UBERON:0001476	94.78	gold quality
eye	UBERON:0000970	94.77	gold quality
ventral tegmental area	UBERON:0002691	94.77	gold quality
subthalamic nucleus	UBERON:0001906	94.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	404.38
E-MTAB-7303	no	116.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

202 targeting DPP8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 18)

• cells overexpressing DP8 exhibit behavioral changesin the presence of ECM components; these effects were independent of enzyme activity (PMID:16700509)
• Dipeptidyl peptidase 8 and dipeptidyl peptidase 9 influence cell-extracellular matrix interactions, and thus may regulate tissue remodeling. (PMID:16704418)
• study has identified the residues absolutely required for the optimal activity of DPP8 and its unique substrate specificity (PMID:17040910)
• DP8 cleavage of the N-terminal two residues of IP10 (CXCL10), ITAC (CXCL11) and SDF-1 (CXCL12), is reported. (PMID:18275857)
• DP8 and DP9 tissue and cellular expression (PMID:19581630)
• DPP8 and DPP9 prevail over canonical DPP-IV/CD26 and FAPalpha in all examined meningioma patients (PMID:20043068)
• This is the first study to demonstrate the presence of DP8 in chronic lymphocytic leukemia (CLL) and the upregulation of DP8 mRNA in CLL. (PMID:20534982)
• Data identify modification points in the topology of a representative DPP8/9-inhibitor, capable of rendering selectivity for DPP8 over DPP9. (PMID:21711053)
• this study demonstrates for the first time that DP8 and DP9 are expressed in breast and ovarian carcinoma cell lines (PMID:22736146)
• analysis of dipeptidyl peptidases 8 and 9 reveals that they may have compensatory roles (PMID:23519473)
• DPP8 was found in macrophages of carotid atherosclerotic plaque and may play a role in disease progression. (PMID:23608773)
• Suggest roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis. (PMID:23704821)
• The SUMO1-E67 interacting loop peptide is an allosteric inhibitor of the dipeptidyl peptidases 8 and 9. (PMID:24072711)
• The DPP8 expressing cell model system is a very useful and promising system for investigating the selectivity and associated toxicity of DPP4 inhibitors on DPP8. (PMID:25464020)
• Data show when cells were treated with siRNA-dipeptidyl peptidase 8 (DPP8), the expression of cyclin D1, matrix metalloproteinases, secreted MMP2 and MMP9 was downregulated. (PMID:30225951)
• Decrease of the pro-inflammatory M1-like response by inhibition of dipeptidyl peptidases 8/9 in THP-1 macrophages - quantitative proteomics of the proteome and secretome. (PMID:32998073)
• Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells. (PMID:33932609)
• DPP8/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathways. (PMID:38458339)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dpp8	ENSMUSG00000032393
rattus_norvegicus	Dpp8	ENSRNOG00000019105
drosophila_melanogaster	CG3744	FBGN0039240
caenorhabditis_elegans	dpf-3	WBGENE00001056

Paralogs (6): FAP (ENSG00000078098), DPP6 (ENSG00000130226), DPP9 (ENSG00000142002), APEH (ENSG00000164062), DPP10 (ENSG00000175497), DPP4 (ENSG00000197635)

Protein

Protein identifiers

Dipeptidyl peptidase 8 — Q6V1X1 (reviewed: Q6V1X1)

Alternative names: Dipeptidyl peptidase IV-related protein 1, Dipeptidyl peptidase VIII, Prolyl dipeptidase DPP8

All UniProt accessions (8): Q6V1X1, H0YK36, H0YKA2, H0YMV1, H0YN53, H3BNM2, H3BQ40, J3KPT0

UniProt curated annotations — full annotation on UniProt →

Function. Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8. Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation. The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition.

Subunit / interactions. Homodimer. Forms a ternary complex with NLRP1, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus). Forms a ternary complex with CARD8, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus). In the ternary complex, only one subunit of the DPP8 homodimer is bound to NLRP1 or CARD8.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed, with highest levels in testis, placenta, prostate, muscle and brain.

Activity regulation. Inhibited by zinc. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate. Specifically inhibited by isoindoline derivatives. Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages.

Induction. In activated T-cells.

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

Isoforms (6)

UniProt ID	Names	Canonical?
Q6V1X1-1	1	yes
Q6V1X1-2	2
Q6V1X1-3	3
Q6V1X1-4	4
Q6V1X1-5	5
Q6V1X1-6	6

RefSeq proteins (6): NP_001307804, NP_001307805, NP_060213, NP_569118, NP_932064, NP_932065 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001375	Peptidase_S9_cat	Domain
IPR002469	Peptidase_S9B_N	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR045785	Dpp_8/9_N	Domain
IPR050278	Serine_Prot_S9B/DPPIV	Family

Pfam: PF00326, PF00930, PF19520

UniProt features (114 total): strand 54, helix 23, turn 11, sequence conflict 10, mutagenesis site 7, splice variant 5, active site 3, chain 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
6EOP	X-RAY DIFFRACTION	2.4
7OR4	X-RAY DIFFRACTION	2.44
7AYQ	X-RAY DIFFRACTION	2.45
6EOO	X-RAY DIFFRACTION	2.5
6HP8	X-RAY DIFFRACTION	2.5
7SVO	X-RAY DIFFRACTION	2.58
7OZ7	X-RAY DIFFRACTION	2.6
7A3K	X-RAY DIFFRACTION	2.65
7AYR	X-RAY DIFFRACTION	2.69
7SVM	X-RAY DIFFRACTION	2.69
7A3G	X-RAY DIFFRACTION	2.8
7A3I	X-RAY DIFFRACTION	2.8
7A3L	X-RAY DIFFRACTION	2.8
6TRW	X-RAY DIFFRACTION	3
7A3J	X-RAY DIFFRACTION	3
6EOS	X-RAY DIFFRACTION	3.1
6QZW	X-RAY DIFFRACTION	3.2
6TRX	X-RAY DIFFRACTION	3.2
6EOT	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6V1X1-F1	90.68	0.80

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): 755 (charge relay system); 833 (charge relay system); 865 (charge relay system)

Mutagenesis-validated functional residues (7):

Position	Phenotype
451	reduced dimerization and reduced enzyme activity.
755	abolishes activity; no effect on subcellular location.
788	strongly reduced enzyme activity.
788	loss of enzyme activity. loss of dimerization.
833	abolishes activity; no effect on subcellular location.
865	abolishes activity; no effect on subcellular location.
275	13-fold reduction in affinity for ala-pro-afc; no effect on subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, CATRRAGC_UNKNOWN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, PU1_Q6, ELK1_01, NRF2_01, RGAGGAARY_PU1_Q6, NERF_Q2, CETS1P54_01, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, GOBP_PROTEOLYSIS, CHEN_HOXA5_TARGETS_9HR_UP, SCGGAAGY_ELK1_02

GO Biological Process (8): proteolysis (GO:0006508), apoptotic process (GO:0006915), immune response (GO:0006955), negative regulation of programmed cell death (GO:0043069), protein maturation (GO:0051604), CARD8 inflammasome complex assembly (GO:0140633), pyroptotic cell death (GO:0141201), NLRP1 inflammasome complex assembly (GO:1904784)

GO Molecular Function (6): aminopeptidase activity (GO:0004177), serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	3
protein metabolic process	2
canonical inflammasome complex assembly	2
exopeptidase activity	2
cellular anatomical structure	2
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
response to stimulus	1
regulation of programmed cell death	1
negative regulation of cellular process	1
gene expression	1
pyroptotic inflammatory response	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPP8	PREP	P48147	950
DPP8	DPP7	Q9UHL4	878
DPP8	TFDP3	Q5H9I0	849
DPP8	HRK	O00198	755
DPP8	APC	P25054	663
DPP8	CARD8	Q9Y2G2	621
DPP8	GCG	P01275	552
DPP8	NLRP1	Q9C000	511
DPP8	GIP	P09681	486
DPP8	GSDMD	P57764	476
DPP8	IGDCC4	Q8TDY8	471
DPP8	PRCP	P42785	466
DPP8	DPP10	Q8N608	458
DPP8	DPP4	P27487	446
DPP8	CXCL1	P09341	438

IntAct

44 interactions, top by confidence:

A	B	Type	Score
ATF2	JUN	psi-mi:“MI:0914”(association)	0.950
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
RIN1	RAP2B	psi-mi:“MI:0914”(association)	0.640
UBXN4	UBE4A	psi-mi:“MI:0914”(association)	0.620
DPP8	COA7	psi-mi:“MI:0915”(physical association)	0.560
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
CCL22	PLXNA2	psi-mi:“MI:0914”(association)	0.530
DPP8	SNRPB	psi-mi:“MI:0914”(association)	0.530
DPP8	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL12	DPP8	psi-mi:“MI:0407”(direct interaction)	0.440
DPP8	CXCL10	psi-mi:“MI:0407”(direct interaction)	0.440
DPP8	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
DPP8	STX1A	psi-mi:“MI:0915”(physical association)	0.400
DPP8	ECE1	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
DOK3	BLTP3B	psi-mi:“MI:0914”(association)	0.350
DPP8	KRBA1	psi-mi:“MI:0914”(association)	0.350
WDR90	CLUH	psi-mi:“MI:0914”(association)	0.350
ICAM4	ATE1	psi-mi:“MI:0914”(association)	0.350
PIGQ	HSPA8	psi-mi:“MI:0914”(association)	0.350
IL17A	ATP1A3	psi-mi:“MI:0914”(association)	0.350
IRAK3	CD44	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), DPP8 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QP51, E9PYK3, E9Q4Z2, G1SPE9, O00763, O15228, O23617, P13676, P13798, P19205, P25154, P35574, P80227, P83006, P98192, Q10MJ1, Q2PQH8, Q338C0, Q496Z0, Q5EBA1, Q5IH13, Q5IH14, Q5R5S1, Q5U5V2, Q5ZIB9, Q641Y5, Q6V1X1, Q6YXW6, Q80YA7, Q80YD1, Q80ZK9, Q86TI2, Q8BVG4, Q8C0P5, Q8C5P5, Q8IYB8, Q8K4M9, Q8N5D0, Q8R146, Q8VZF3

Diamond homologs: A0A2R8QP51, A1CHP1, A1CJQ1, A1D7R6, A2QEK7, A4QYQ5, A6SL49, A7EQZ1, B0XYK8, B1A4F7, B2A951, B2RJX3, B2WC36, B6QVW4, B8MTH6, B8N076, C1GT79, C4JHY5, C5FYZ3, C7YYG9, D1Z9B4, D4AQT0, E3QKD2, E3S9K3, E4UYL6, E9ETL5, Q0CXB1, Q0IXP9, Q18253, Q2HF90, Q2UPW4, Q4WX13, Q6V1X1, Q7JKY3, Q7MUW6, Q7SHU8, Q80YA7, Q86TI2, Q8BVG4, Q96VT7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
SARS-CoV-1-host interactions	5	20.4×	2e-04
SARS-CoV-2-host interactions	6	16.6×	1e-04
SARS-CoV-1 Infection	5	16.6×	4e-04
SARS-CoV-2 Infection	6	11.2×	4e-04
Signaling by Interleukins	7	10.4×	2e-04
Transcriptional Regulation by TP53	7	10.1×	2e-04
SARS-CoV Infections	7	9.0×	4e-04
Cytokine Signaling in Immune system	8	7.6×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
chemotaxis	5	13.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3271 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65450992:AACT:A	donor_loss	1.0000
15:65450993:ACTC:A	donor_loss	1.0000
15:65450994:CTC:C	donor_loss	1.0000
15:65450995:TCA:T	donor_loss	1.0000
15:65450996:CACC:C	donor_loss	1.0000
15:65450997:ACCTG:A	donor_loss	1.0000
15:65450998:C:CG	donor_loss	1.0000
15:65451958:A:AC	donor_gain	1.0000
15:65451959:C:CT	donor_gain	1.0000
15:65451959:CT:C	donor_gain	1.0000
15:65454261:A:AG	donor_loss	1.0000
15:65454261:AC:A	donor_gain	1.0000
15:65454262:C:CT	donor_loss	1.0000
15:65454262:CC:C	donor_gain	1.0000
15:65454414:CC:C	acceptor_gain	1.0000
15:65454415:CC:C	acceptor_gain	1.0000
15:65454415:CCT:C	acceptor_loss	1.0000
15:65454416:C:CC	acceptor_gain	1.0000
15:65454416:CTGT:C	acceptor_loss	1.0000
15:65454417:T:C	acceptor_loss	1.0000
15:65455753:A:AC	donor_gain	1.0000
15:65455754:C:CC	donor_gain	1.0000
15:65463768:C:CT	donor_gain	1.0000
15:65466809:CAGTG:C	acceptor_gain	1.0000
15:65466814:C:CC	acceptor_gain	1.0000
15:65467065:TAATA:T	donor_loss	1.0000
15:65467066:AATAC:A	donor_gain	1.0000
15:65467067:ATACC:A	donor_loss	1.0000
15:65467068:TACC:T	donor_loss	1.0000
15:65467069:ACCT:A	donor_loss	1.0000

AlphaMissense

5810 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65446986:G:C	H865Q	1.000
15:65446986:G:T	H865Q	1.000
15:65446987:T:C	H865R	1.000
15:65446988:G:C	H865D	1.000
15:65446990:C:A	R864I	1.000
15:65451066:A:T	V836D	1.000
15:65451068:A:C	N835K	1.000
15:65451068:A:T	N835K	1.000
15:65451070:T:C	N835D	1.000
15:65451075:T:A	D833V	1.000
15:65451075:T:G	D833A	1.000
15:65451076:C:A	D833Y	1.000
15:65451076:C:G	D833H	1.000
15:65451084:C:T	G830D	1.000
15:65452041:C:G	R794P	1.000
15:65452042:G:T	R794S	1.000
15:65452051:A:G	Y791H	1.000
15:65452072:A:G	W784R	1.000
15:65452072:A:T	W784R	1.000
15:65452090:C:A	G778W	1.000
15:65454309:C:T	G758E	1.000
15:65454312:C:A	G757V	1.000
15:65454312:C:T	G757E	1.000
15:65454319:A:G	S755P	1.000
15:65454322:A:G	W754R	1.000
15:65454322:A:T	W754R	1.000
15:65454324:C:A	G753V	1.000
15:65454324:C:T	G753D	1.000
15:65454325:C:G	G753R	1.000
15:65454339:C:G	R748P	1.000

dbSNP variants (sampled 300 via entrez): RS1000005843 (15:65465833 C>A,G,T), RS1000008225 (15:65470288 CTT>C), RS1000013622 (15:65470698 C>CA), RS1000096063 (15:65494517 T>A), RS1000106917 (15:65466068 T>C), RS1000151750 (15:65446047 G>C), RS1000154722 (15:65459459 C>T), RS1000167906 (15:65471985 G>A), RS1000213403 (15:65444222 G>A), RS1000243481 (15:65459825 C>A,T), RS1000271685 (15:65511124 T>C), RS1000311723 (15:65486992 TA>T,TAA), RS1000393818 (15:65497717 C>T), RS1000438688 (15:65492239 G>C), RS1000490160 (15:65451516 A>G)

Disease associations

OMIM: gene MIM:606819 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000587_7	Mean corpuscular hemoglobin	3.000000e-09
GCST004608_198	Granulocyte percentage of myeloid white cells	4.000000e-15
GCST004609_215	Monocyte percentage of white cells	1.000000e-15
GCST004625_152	Monocyte count	6.000000e-09
GCST005996_1	Red blood cell count	3.000000e-08
GCST006979_928	Heel bone mineral density	1.000000e-15
GCST010083_124	Hemoglobin levels	3.000000e-11
GCST90002380_31	Basophil percentage of white cells	7.000000e-14
GCST90002390_416	Mean corpuscular hemoglobin	2.000000e-49
GCST90002391_149	Mean corpuscular hemoglobin concentration	3.000000e-66
GCST90002392_429	Mean corpuscular volume	1.000000e-37
GCST90002396_636	Mean reticulocyte volume	9.000000e-30
GCST90002403_487	Red blood cell count	2.000000e-44

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004305	erythrocyte count
EFO:0009270	heel bone mineral density
EFO:0007992	basophil percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885564 (PROTEIN FAMILY), CHEMBL4657 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 84,552 (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
CHEMBL1422	SITAGLIPTIN	4	26,582
CHEMBL142703	VILDAGLIPTIN	4	20,312
CHEMBL2147777	TENELIGLIPTIN	4	1,406
CHEMBL237500	LINAGLIPTIN	4	5,282
CHEMBL385517	SAXAGLIPTIN ANHYDROUS	4	18,553
CHEMBL515387	GOSOGLIPTIN	4	785
CHEMBL67279	TALABOSTAT	3	10,259
CHEMBL4296719	DUTOGLIPTIN	3	1,373

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S9: Prolyl oligopeptidase

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
talabostat	Inhibition	8.82	pKi
compound 18 [PMID: 15664838]	Inhibition	7.9	pIC50
1G244	Inhibition	7.85	pIC50
ICeD-2	Inhibition	7.62	pIC50
tominostat	Inhibition	7.49	pIC50
teneligliptin	Inhibition	6.59	pIC50
compound 24dd [PMID: 20684603]	Inhibition	6.57	pKi
compound 42 [PMID: 37721854]	Inhibition	6.22	pIC50
vildagliptin	Inhibition	5.66	pIC50
compound 9 [PMID: 20718420]	Inhibition	5.43	pIC50

Binding affinities (BindingDB)

398 measured of 483 human assays (484 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
UAMC-000-5364	IC50	0.001 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5377	IC50	0.005 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5376	IC50	0.005 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5366	IC50	0.006 nM	US-20250353833: DPP9 BINDING COMPOUNDS
2-[2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]ethoxy]ethyl N-[3-[[2-(5,6-difluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamate	IC50	0.007 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5380	IC50	0.008 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5379	IC50	0.009 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5111	IC50	0.051 nM	US-20250353833: DPP9 BINDING COMPOUNDS
2-[2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]ethoxy]ethyl N-[3-[[2-(5-fluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamate	IC50	0.066 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5215	IC50	0.094 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5114	IC50	0.102 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5365	IC50	0.117 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5113	IC50	0.127 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5382	IC50	0.127 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5112	IC50	0.145 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5360	IC50	0.161 nM	US-20250353833: DPP9 BINDING COMPOUNDS
2-[2-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]ethoxy]ethyl N-[3-[[2-(5,6-difluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamate	IC50	0.21 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5116	IC50	0.222 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5361	IC50	0.244 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5363	IC50	0.27 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5035	IC50	0.276 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5359	IC50	0.295 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5357	IC50	0.403 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5378	IC50	0.476 nM	US-20250353833: DPP9 BINDING COMPOUNDS
N-[2-[2-[[3-[[2-(5,6-difluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamoylamino]ethoxy]ethyl]-5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanamide	IC50	0.541 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5356	IC50	0.757 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5381	IC50	0.793 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5032	IC50	0.812 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5156	IC50	0.835 nM	US-20250353833: DPP9 BINDING COMPOUNDS
2-[2-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethoxy]ethyl N-[3-[[2-(5,6-difluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamate	IC50	0.876 nM	US-20250353833: DPP9 BINDING COMPOUNDS
(2S)-1-[(2S)-2-amino-2-cyclopentylacetyl]pyrrolidine-2-carbonitrile	KI	1 nM
2-[4-{{2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid	KI	1 nM
US20250353833, Inhibitor MFE-2022-136	IC50	1.12 nM	US-20250353833: DPP9 BINDING COMPOUNDS
6-[4-({2-[(2S,5R)-2-cyano-5-ethynylpyrrolidin-1-yl]-2-oxoethyl}amino)-4-methylpiperidin-1-yl]pyridine-3-carboxylic acid	KI	1.3 nM
(1S,6R)-3-{[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[3,4-a]pyrazin-7-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	1.3 nM
UAMC-000-50 37	IC50	1.3 nM	US-20250353833: DPP9 BINDING COMPOUNDS
UAMC-000-5036	IC50	1.33 nM	US-20250353833: DPP9 BINDING COMPOUNDS
(3R, 4R)-1-(6-(3, 3-Difluoropyrrolidin-1-yl)pyrimidin-4-yl)-4-(2, 4, 5-trifluorophenyl)piperidin-3-amine	KI	1.6 nM
3-{6-[(3R,4S)-3-amino-4-(2,4,5-trifluorophenyl)pyrrolidin-1-yl]pyrimidin-4-yl}benzoic acid	KI	1.8 nM
Xanthine mimetic compound 6	KI	2 nM
2-{[2-(3-aminopiperidin-1-yl)-5-methyl-4,6-dioxo-1H,4H,5H,6H-pyrrolo[3,4-d]imidazol-1-yl]methyl}benzonitrile	KI	2 nM
(3R,4S)-1-[4-(3-methanesulfonylphenyl)-1,3,5-triazin-2-yl]-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	2.1 nM
(R)-1-(6-((3R,4R)-3-Amino-4-(2,4,5-trifluorophenyl)piperidin-1-yl)pyrimidin-4-yl)pyrrolidin-3-ol	KI	2.3 nM
ABT-279 analogue	KI	3 nM
(3R,4S)-1-{6-[3-(morpholine-4-sulfonyl)phenyl]pyrimidin-4-yl}-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	3.2 nM
Racemic mixture	KI	3.2 nM
(3R,4S)-1-[6-(3-methanesulfonylphenyl)pyrimidin-4-yl]-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	3.4 nM
(1S,6R)-3-(3-carbamoylphenoxymethyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	3.6 nM
3-{2-[(4R,5R)-5-amino-2-oxo-4-(2,4,5-trifluorophenyl)piperidin-1-yl]ethyl}benzoic acid	KI	3.8 nM
6-{[4-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)cyclohexyl]oxy}pyridine-3-carbonitrile	KI	4 nM

ChEMBL bioactivities

786 potent at pChembl≥5 of 1284 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.07	Ki	0.086	nM	CHEMBL1215374
9.57	Ki	0.27	nM	CHEMBL1215376
9.40	Ki	0.4	nM	CHEMBL1215167
9.38	Ki	0.42	nM	CHEMBL1215087
9.24	Ki	0.58	nM	CHEMBL1215448
9.22	Ki	0.6	nM	CHEMBL1215375
9.19	Ki	0.65	nM	CHEMBL1215302
9.15	Ki	0.7	nM	CHEMBL1215089
9.10	Ki	0.8	nM	CHEMBL2441846
9.02	Ki	0.95	nM	CHEMBL1215236
9.00	Ki	1	nM	CHEMBL2441955
9.00	Ki	1	nM	CHEMBL2441844
8.96	Ki	1.1	nM	CHEMBL1215164
8.96	Ki	1.1	nM	CHEMBL1215299
8.92	IC50	1.2	nM	CHEMBL2063040
8.92	Ki	1.2	nM	CHEMBL1215301
8.89	Ki	1.3	nM	CHEMBL1215017
8.89	Ki	1.3	nM	CHEMBL1215233
8.85	Ki	1.4	nM	CHEMBL2441954
8.85	Ki	1.4	nM	CHEMBL2441839
8.85	Ki	1.4	nM	CHEMBL1215300
8.82	Ki	1.5	nM	TALABOSTAT
8.77	Ki	1.7	nM	CHEMBL2441837
8.77	Ki	1.7	nM	CHEMBL1214877
8.77	Ki	1.7	nM	CHEMBL1215166
8.74	Ki	1.8	nM	CHEMBL2441845
8.73	IC50	1.85	nM	VILDAGLIPTIN
8.72	Ki	1.9	nM	CHEMBL1214876
8.70	Ki	2	nM	CHEMBL2441953
8.70	Ki	2	nM	CHEMBL63860
8.70	Ki	2	nM	CHEMBL1215018
8.66	Ki	2.2	nM	CHEMBL1214942
8.66	Ki	2.2	nM	CHEMBL1214944
8.66	Ki	2.2	nM	CHEMBL1215088
8.66	Ki	2.2	nM	CHEMBL1215373
8.64	Ki	2.3	nM	CHEMBL1215090
8.62	Ki	2.4	nM	CHEMBL1214943
8.60	Ki	2.5	nM	CHEMBL2441844
8.60	Ki	2.5	nM	CHEMBL1215235
8.55	Ki	2.8	nM	CHEMBL2441829
8.55	Ki	2.8	nM	CHEMBL1215016
8.54	Ki	2.9	nM	CHEMBL1215163
8.52	IC50	3	nM	CHEMBL6060914
8.51	Ki	3.1	nM	CHEMBL67089
8.42	Ki	3.8	nM	CHEMBL2441848
8.42	Ki	3.8	nM	CHEMBL2441841
8.42	Ki	3.8	nM	CHEMBL2441830
8.41	Ki	3.9	nM	CHEMBL2441847
8.41	Ki	3.9	nM	CHEMBL2441838
8.41	Ki	3.9	nM	CHEMBL2441830

PubChem BioAssay actives

785 with measured affinity, of 2638 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
1-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-2-[(6-methyl-2-pyridinyl)methylamino]ethanone	499233: Inhibition of human DPP8	ki	0.0001	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-2-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0003	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-(4-methylsulfonylpiperazin-1-yl)methanone	499233: Inhibition of human DPP8	ki	0.0004	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(pyridin-3-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0004	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(4-pyridin-3-yl-1,3-thiazol-2-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0006	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-3-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0006	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-4-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0006	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(2,5-dimethylpyrazol-3-yl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0007	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylacetamide	778688: Inhibition of DPP8 (unknown origin)	ki	0.0008	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(2-pyridin-2-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0009	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-(2-oxo-2-piperidin-1-ylethyl)-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0010	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]acetic acid	778688: Inhibition of DPP8 (unknown origin)	ki	0.0010	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-(4,4-dimethyl-1,3-oxazolidin-3-yl)methanone	499233: Inhibition of human DPP8	ki	0.0011	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0011	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(furan-2-ylmethyl)-N,7-dimethylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0012	uM
[(2R,4S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]-4-hydroxypyrrolidin-2-yl]boronic acid	675169: Inhibition of human DPP8 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins	ic50	0.0012	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methanone	499233: Inhibition of human DPP8	ki	0.0013	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(2-ethylpyrazol-3-yl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0013	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-[[(2S)-oxolan-2-yl]methyl]-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0014	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-(2-oxo-2-pyrrolidin-1-ylethyl)-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0014	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(furan-2-ylmethyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0014	uM
[(2R)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid	390967: Inhibition of human recombinant DPP8 expressed in HEK293T cells	ki	0.0015	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-[(2S)-1-methoxypropan-2-yl]-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0017	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(1,2-oxazol-3-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0017	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,N-diethyl-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0017	uM
3-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]propanoic acid	778688: Inhibition of DPP8 (unknown origin)	ki	0.0018	uM
ethyl 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylate	499233: Inhibition of human DPP8	ki	0.0019	uM
(2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile	1781442: Inhibition of human recombinant DPP8 using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by fluorescence based microplate reader assay	ic50	0.0019	uM
[(2R)-1-[(2S)-2-aminopropanoyl]pyrrolidin-2-yl]boronic acid	390967: Inhibition of human recombinant DPP8 expressed in HEK293T cells	ki	0.0020	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N-methyl-N-propylacetamide	778688: Inhibition of DPP8 (unknown origin)	ki	0.0020	uM
N-[(3S)-1-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carbonyl]pyrrolidin-3-yl]methanesulfonamide	499233: Inhibition of human DPP8	ki	0.0020	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-pyrrolidin-1-ylmethanone	499233: Inhibition of human DPP8	ki	0.0022	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(2-methylsulfonylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0022	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-[2-(1H-imidazol-5-yl)ethyl]-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0022	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(oxan-4-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0022	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(4-methyl-1,3-thiazol-2-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0023	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-morpholin-4-ylmethanone	499233: Inhibition of human DPP8	ki	0.0024	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(thiophen-2-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0025	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(4-methoxyphenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0028	uM
4-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carbonyl]piperazin-2-one	499233: Inhibition of human DPP8	ki	0.0028	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(1,3-oxazol-2-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0029	uM
[(2R)-1-(2-aminoacetyl)pyrrolidin-2-yl]boronic acid	390967: Inhibition of human recombinant DPP8 expressed in HEK293T cells	ki	0.0031	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0038	uM
(2R)-2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylpropanamide	778688: Inhibition of DPP8 (unknown origin)	ki	0.0038	uM
3-(aminomethyl)-6-[[(2S)-1-cyclopropylsulfonylpyrrolidin-2-yl]methyl]-4-(2,4-dichlorophenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0038	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-[[(2R)-oxolan-2-yl]methyl]-7H-pyrrolo[3,4-b]pyridin-5-one	778688: Inhibition of DPP8 (unknown origin)	ki	0.0039	uM
3-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylpropanamide	778688: Inhibition of DPP8 (unknown origin)	ki	0.0039	uM
(2S)-1-[(2S)-2-amino-2-cyclopentylacetyl]pyrrolidine-2-carbonitrile	1796772: DPP Inhibition Assay from Article 10.1021/bi060184f: “Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors.”	ki	0.0040	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(1-methylpyrazol-3-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499233: Inhibition of human DPP8	ki	0.0041	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N-methylacetamide	778688: Inhibition of DPP8 (unknown origin)	ki	0.0043	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
glycylproline 4-nitroanilide	affects cotreatment, decreases activity, decreases cleavage	1
alanylproline-4-nitroanilide	increases cleavage, affects cotreatment, decreases activity, decreases cleavage	1
CGP 52608	affects binding, increases reaction	1
UAMC00132	decreases activity, affects cotreatment, decreases cleavage	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Vildagliptin	decreases activity	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Zinc	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

163 unique, capped per target: 156 binding, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3873291	Binding	Inhibition of full length recombinant human DPP-8/9 expressed in HEK293 cells at 10 uM incubated for 1 hr	Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents. — Eur J Med Chem
CHEMBL4683607	ADMET	Inhibition of recombinant human DPP8/9 expressed in Rosetta cells at 10 uM using Gly-Pro-p-nitroanilide as substrate incubated for 1 hr relative to control	The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1MC	Abcam K-562 DPP8 KO	Cancer cell line	Female
CVCL_D2IX	Abcam Raji DPP8 KO	Cancer cell line	Male
CVCL_UQ44	Abcam Jurkat DPP8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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