CPB2

Summary

CPB2 (carboxypeptidase B2, HGNC:2300) is a protein-coding gene on chromosome 13q14.13, encoding Carboxypeptidase B2 (Q96IY4). Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities.

Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by trypsin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and its promoter region. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 1361 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2300
Approved symbol	CPB2
Name	carboxypeptidase B2
Location	13q14.13
Locus type	gene with protein product
Status	Approved
Aliases	CPU, PCPB, TAFI
Ensembl gene	ENSG00000080618
Ensembl biotype	protein_coding
OMIM	603101
Entrez	1361

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 nonsense_mediated_decay

ENST00000181383, ENST00000439329, ENST00000674625, ENST00000675730, ENST00000882315, ENST00000882316, ENST00000882317, ENST00000882318, ENST00000882319, ENST00000882320, ENST00000882321, ENST00000882322, ENST00000882323, ENST00000882324, ENST00000882325, ENST00000882326, ENST00000882327, ENST00000882328, ENST00000882329, ENST00000882330, ENST00000882331, ENST00000882332, ENST00000882333, ENST00000882334

RefSeq mRNA: 2 — MANE Select: NM_001872 NM_001278541, NM_001872

CCDS: CCDS73568, CCDS9401

Canonical transcript exons

ENST00000181383 — 11 exons

Exon	Start	End
ENSE00000462952	46087745	46087820
ENSE00000462954	46082441	46082549
ENSE00000682158	46073873	46073977
ENSE00000682165	46084219	46084343
ENSE00000836753	46055762	46055849
ENSE00000836755	46058179	46058381
ENSE00000836757	46064648	46064741
ENSE00000836759	46067307	46067417
ENSE00000836761	46078800	46078901
ENSE00002817524	46104936	46105033
ENSE00003844263	46053186	46053798

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 99.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.7540 / max 1317.1362, expressed in 20 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137157	3.6736	20
137158	0.0805	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.27	gold quality
liver	UBERON:0002107	99.13	gold quality
lower lobe of lung	UBERON:0008949	85.96	gold quality
corpus epididymis	UBERON:0004359	80.11	gold quality
cauda epididymis	UBERON:0004360	78.66	gold quality
right lung	UBERON:0002167	76.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.38	gold quality
lung	UBERON:0002048	75.05	gold quality
gall bladder	UBERON:0002110	74.26	gold quality
upper lobe of lung	UBERON:0008948	72.44	gold quality
upper lobe of left lung	UBERON:0008952	71.20	gold quality
visceral pleura	UBERON:0002401	69.10	gold quality
caput epididymis	UBERON:0004358	64.57	gold quality
corpus callosum	UBERON:0002336	61.22	gold quality
adrenal tissue	UBERON:0018303	57.35	gold quality
colonic epithelium	UBERON:0000397	56.39	gold quality
ileal mucosa	UBERON:0000331	54.02	silver quality
body of pancreas	UBERON:0001150	54.00	gold quality
oocyte	CL:0000023	53.18	gold quality
pleura	UBERON:0000977	50.91	silver quality
tibialis anterior	UBERON:0001385	50.47	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.37	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
thymus	UBERON:0002370	50.29	silver quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
buccal mucosa cell	CL:0002336	50.07	gold quality
vastus lateralis	UBERON:0001379	49.57	gold quality
medial globus pallidus	UBERON:0002477	49.40	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	58.54
E-MTAB-6386	no	11.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPG, HNF1A, JUN, NR3C1

miRNA regulators (miRDB)

26 targeting CPB2, 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-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-562	97.66	65.63	698
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-8086	97.21	64.13	331
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946
HSA-MIR-4661-3P	96.81	66.02	342

Literature-anchored findings (GeneRIF, showing 40)

• Weinvestigated the role of TAFI in haemophilia A by measuring the clot lysis times of tissue-factor-induced fibrin formation and tPA mediated fibrinolysis. (PMID:11686321)
• Protein S inhibits TAFI activation in two ways. (PMID:11686322)
• PCI can up regulate TAFI activation by inhibiting the protein C activation. PCI may therefore be an important regulator in the balance between coagulation and fibrinolysis by differentially inhibiting the activation of TAFI and of protein C. (PMID:11686324)
• Ala147Thr and C+1542G polymorphisms in the TAFI gene are not asssociated with a higher risk of venous thrombosis in FV Leiden carriers. (PMID:11776333)
• residues in the P6-P'3 region of TAFI do not determine the thrombomodulin dependence of activation (PMID:11786552)
• TAFI may provide a link between coagulation and blood pressure regulation (PMID:11903334)
• There is an association between levels and activated protein C in normotensive type 2 diabetic patients. (PMID:12087030)
• TAFIa is increased in patients with APC resistance due to FV Leiden mutation, indicating that downregulation of fibrinolysis may be a factor in thrombosis. (PMID:12165290)
• Decreased TAFI does not contribute to the impairment of fibrinolysis in patients with preeclampsia and/or intrauterine fetal growth retardation. (PMID:12362237)
• TAFI may play a role in the development of venous thromboembolism in factor V Leiden carriers (PMID:12368162)
• increased plasma level of TAFI may be involved in the mechanism of vascular endothelial damage in patients with type 2 diabetes mellitus. (PMID:12574207)
• results establish the presence of thrombin activatable fibrinolysis inhibitor(TAFI) in platelets and suggest a role for platelet-derived TAFI in the protection of the clot against fibrinolysis (PMID:12595308)
• Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and angina pectoris incidence. (PMID:12624641)
• there is a functional glucocorticoid response element (GRE) in the human TAFI promoter which is capable of binding the glucocorticoid receptor (PMID:12645517)
• mutations in substrate binding site alter its substrate specificity (PMID:12799375)
• plasma hyperfibrinolysis in cirrhosis is largely due to a defective TAFIa generation resulting from low TAFI levels and probably from impaired thrombin gener (PMID:12830006)
• Plasma levels of TAFI were not elevated in pulmonary embolism, except in cases with a high clot burden, suggesting that TAFI levels might be secondarily increased by release from activated platelets. (PMID:12871455)
• TAFI gene polymorphisms (Ala147Thr, Thr325Ile and -438A/G) in both promoter & coding regions seem to be involved (both independently & additively) in the regulation of plasma TAFI Ag levels suggesting regulation on both transcriptional & protein levels. (PMID:12876631)
• TAFIa inhibited lysis of model thrombi and plasma clots by uPA, scuPA and tPA, which could be partially overcome by plasminogen, consistent with TAFIa exerting its effect through modifying the binding of plasminogen and tPA to fibrin. (PMID:12941043)
• investigate the hypothesisis that TAFI -438 G/A and factor XIIIA Val34Leu polymorphisms might influence the formation and fate of emboli and accordingly the risk of pulmonary embolism in a case control study (PMID:12958613)
• investigated hypothesis that hyperbaric exposure increases fibrinolytic activity; hyperbaric exposure followed by decompression did not alter TAFI level in blood (PMID:14517491)
• examined the effect of activated TAFI in modulating the proinflammatory functions (e.g.,cell adhesion, neutrophil activation) of bradykinin, complement C5a, and thrombin-cleaved osteopontin (PMID:14525995)
• a novel mechanism was identified whereby TAFIa can modulate plasmin levels by increasing the susceptibility of plasmin to inhibition by antiplasmin. (PMID:14715654)
• prevalence of the Thr325Ile dimorphism in the TAFI gene in 50 patients who survived meningococcal disease, in 176 first-degree relatives of a consecutive patient series with meningococcal disease and 212 controls from the same geographic region (PMID:14717966)
• A high TAFI level was associated with a 2-fold higher risk for recurrence of thrombosis; data also support the concept of a linkage between fibrinolysis and the coagulation system (PMID:14739223)
• thrombin activatable fibrinolysis inhibitor (TAFI) activity seemed to increase progressively until around 20 weeks of gestation, then maintained a moderately elevated level until delivery, and promptly decreased after delivery (PMID:15004439)
• TAFI has a role in coagulation and fibrinolysis, and could be targeted with antifibrinolytic agents [editorial] (PMID:15025077)
• the down-regulation of fibrinolysis mediated by basic carboxypeptidase B involves a threshold mechanism (PMID:15128744)
• study suggests that thrombin-activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients (PMID:15224354)
• TAFI levels increased significantly at 24- and 72-hour time points in burn, septic injury, and burn+septic injury groups (PMID:15497025)
• there is a significant increase in TAFI levels, which translates into increased clot lysis time during pregnancy; changes in TAFI contribute to the increasing APCR of pregnancy (PMID:15543330)
• IL-1beta plus IL-6 decreased stability of the TAFI transcript produced using the 3’-most polyadenylation site and also resulted in profound shifts in the relative abundances of the respective polyadenylated forms (PMID:15550029)
• High TAFI levels might possibly contribute to the thrombotic tendency in Behcet’s disease. (PMID:15668188)
• Thrombin Activatable Fibrinolysis Inhibitor (TAFI) plays an important role in a delicate balance between coagulation and fibrinolysis determines the stability of the fibrin clot. (PMID:15692247)
• Activation of pro-TAFI by plasmin may be a feedback mechanism that counterbalances increased fibrinolysis in patients with bleeding disorders (PMID:15719893)
• Thrombin-activatable fibrinolysis inhibitor gene polymorphisms are strongly associated to plasma TAFI levels, but their role in coronary heart disease risk is not established in this study (PMID:15978108)
• Metabolic syndrome and hypercholesteremia synsynergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of TAF1, which inhibit fibrinolyaia. (PMID:16123492)
• results of this study showed for the first time that TAFI activity is increased in patients with clonal thrombocytosis (PMID:16244771)
• Results demonstrate the importance of carboxypeptidase U (CPU) stability over proCPU concentration in down-regulating fibrinolysis. (PMID:16441664)
• TAFI concentrations and enhanced thrombin generation in hypertensive kidney transplant recipients may contribute to the hypofibrinolysis and progressive atherosclerosis in this population. (PMID:16504676)

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpb2	ENSDARG00000037144
mus_musculus	Cpb2	ENSMUSG00000021999
rattus_norvegicus	Cpb2	ENSRNOG00000010935
drosophila_melanogaster	CG3097	FBGN0029804
drosophila_melanogaster	CG3108	FBGN0029807
drosophila_melanogaster	CG18585	FBGN0031929
drosophila_melanogaster	CG7025	FBGN0031930
drosophila_melanogaster	CG4017	FBGN0032143
drosophila_melanogaster	CG17633	FBGN0032144
drosophila_melanogaster	CG2915	FBGN0033241
drosophila_melanogaster	CG12374	FBGN0033774
drosophila_melanogaster	CG14820	FBGN0035718
drosophila_melanogaster	CG8563	FBGN0035777
drosophila_melanogaster	CG8562	FBGN0035779
drosophila_melanogaster	CG18417	FBGN0035780
drosophila_melanogaster	CG8560	FBGN0035781
drosophila_melanogaster	CG8539	FBGN0035791
drosophila_melanogaster	CG4408	FBGN0039073
drosophila_melanogaster	CG32379	FBGN0052379
drosophila_melanogaster	CG42264	FBGN0259149
caenorhabditis_elegans		WBGENE00004747
caenorhabditis_elegans	T06A4.1	WBGENE00020281
caenorhabditis_elegans	Y47G6A.19	WBGENE00021645
caenorhabditis_elegans		WBGENE00021984

Paralogs (8): CPA1 (ENSG00000091704), CPA4 (ENSG00000128510), CPO (ENSG00000144410), CPB1 (ENSG00000153002), CPA2 (ENSG00000158516), CPA5 (ENSG00000158525), CPA3 (ENSG00000163751), CPA6 (ENSG00000165078)

Protein

Protein identifiers

Carboxypeptidase B2 — Q96IY4 (reviewed: Q96IY4)

Alternative names: Carboxypeptidase U, Plasma carboxypeptidase B, Thrombin-activable fibrinolysis inhibitor

All UniProt accessions (4): Q96IY4, A0A087WSY5, A0A6Q8PG06, A0A6Q8PHS9

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.

Subcellular location. Secreted.

Tissue specificity. Plasma; synthesized in the liver.

Post-translational modifications. N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4.

Activity regulation. TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-324.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IY4-1	1	yes
Q96IY4-2	2

RefSeq proteins (2): NP_001265470, NP_001863* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR003146	M14A_act_pep	Domain
IPR033849	CPB2	Domain
IPR036990	M14A-like_propep	Homologous_superfamily

Pfam: PF00246, PF02244

Enzyme classification (BRENDA):

• EC 3.4.17.20 — carboxypeptidase U (BRENDA: 12 organisms, 74 substrates, 104 inhibitors, 40 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
HIPPURYL-ARGININE	—	7
P-ANISYLAZOFORMYL-L-ARGININE	0.0002	5
ANISYLAZOFORMYL-LYS	0.979–1.26	4
HIPPURYL-L-ARG	1.12–817	4
HIPPURYL-L-LYS	1.45–933	4
N-[3-(2-FURYLACRYLOYL)]-L-ALA-L-LYS	3.41–280	3
HIPPURYL-ARG	2.38–3.44	2
ARG6-LEU5-ENKEPHALIN	63	1
ARG6-MET5-ENKEPHALIN	140	1
BIOTINYL-(EPSILON-AMINOCAPROIC ACID)-(EPSILON-AM	0.012	1
BRADYKININ	10	1
HIPPURYL-L-ARGININIC ACID	240	1
LYS6-LEU5-ENKEPHALIN	110	1
LYS6-MET5-ENKEPHALIN	220	1
N-BENZOYL-2’-CYANO-L-PHE-L-ARG	0.02	1

UniProt features (67 total): helix 17, strand 16, binding site 8, turn 7, glycosylation site 5, disulfide bond 3, splice variant 2, sequence variant 2, signal peptide 1, propeptide 1, site 1, chain 1, sequence conflict 1, domain 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4P10	X-RAY DIFFRACTION	2
3LMS	X-RAY DIFFRACTION	2.5
7NEE	X-RAY DIFFRACTION	2.55
3D68	X-RAY DIFFRACTION	2.8
7NEU	X-RAY DIFFRACTION	2.8
5HVF	X-RAY DIFFRACTION	2.85
5HVH	X-RAY DIFFRACTION	3
5HVG	X-RAY DIFFRACTION	3.05
3D66	X-RAY DIFFRACTION	3.1
3D67	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IY4-F1	94.32	0.92

Antibody-complex structures (SAbDab): 3 — 5HVF, 5HVG, 5HVH

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 (2): 324–325 (cleavage; by thrombin); 385 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 310; 311–312; 363; 181–184; 181; 184; 239; 256–257

Disulfide bonds (3): 178–191, 250–274, 265–279

Glycosylation sites (5): 44, 73, 85, 108, 241

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins
R-HSA-977606	Regulation of Complement cascade
R-HSA-166658	Complement cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 123 (showing top): MODULE_172, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_WOUND_HEALING, MORF_MSH3, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_COAGULATION, MORF_BRCA1, MORF_RAD51L3, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, MODULE_492, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, MORF_CTSB, GOBP_REGULATION_OF_RESPONSE_TO_WOUNDING

GO Biological Process (4): proteolysis (GO:0006508), blood coagulation (GO:0007596), fibrinolysis (GO:0042730), hemostasis (GO:0007599)

GO Molecular Function (7): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Peptide hormone metabolism	1
Complement cascade	1
Innate Immune System	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
negative regulation of blood coagulation	1
regulation of body fluid levels	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPB2	PLG	P00747	969
CPB2	THBD	P07204	958
CPB2	PLAT	P00750	912
CPB2	SERPINF2	P08697	862
CPB2	SERPINF1	P36955	816
CPB2	CPE	P16870	811
CPB2	F2	P00734	809
CPB2	SERPINE1	P05121	773
CPB2	KNG1	P01042	744
CPB2	PROCR	Q9UNN8	724
CPB2	F3	P13726	719
CPB2	F7	P08709	710
CPB2	KLK4	Q9Y5K2	710
CPB2	PLAU	P00749	708
CPB2	A2M	P01023	697

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TINAG	CPB2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (12): A2M (Reconstituted Complex), CPB2 (Reconstituted Complex), CPB2 (Co-purification), C5 (Biochemical Activity), GALK1 (Co-fractionation), MAT1A (Co-fractionation), MAT2A (Co-fractionation), NDUFS4 (Co-fractionation), NDUFS8 (Co-fractionation), OGT (Co-fractionation), CPB2 (Affinity Capture-MS), TINAG (Two-hybrid)

ESM2 similar proteins: A0A1S4F020, A6XGK3, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4B5N0, D4D675, D4DL57, O02350, O17754, O97397, P00730, P00731, P00732, P09954, P09955, P15085, P15086, P15088, P15089, P16406, P19222, P19223, P21961, P37892, P38836, P42787, P48052, P54969, P55261, Q0II73, Q29NC4, Q2KIG3, Q2KJ83, Q3T905, Q4R7R2, Q504N0

Diamond homologs: A1CSU3, A1DGH9, A2QZA2, A6RCF5, A6XGK3, A7EUC0, B0XRS8, B6H233, B6Q972, B6V865, B8M2K0, B8NBP9, B8XGR3, C0NM08, C0SAI5, C1GDH9, C1HE31, C4JEE1, C5FH26, C5FPR9, C5FVN6, C5G6U8, C5JZS0, C5PHW9, C6H4F1, D4AKU7, D4AS12, D4B5N0, D4D675, D4DIW7, D4DL57, E4UPZ6, E5A0U8, E9DD69, O02350, O74818, P04069, P19223, P38836, P42788

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1689 predictions. Top by Δscore:

Variant	Effect	Δscore
13:46053794:TAGGT:T	acceptor_gain	1.0000
13:46053795:AGGT:A	acceptor_gain	1.0000
13:46053796:GGT:G	acceptor_gain	1.0000
13:46053797:GT:G	acceptor_gain	1.0000
13:46053799:C:CC	acceptor_gain	1.0000
13:46055756:ACT:A	donor_loss	1.0000
13:46055757:CTTAC:C	donor_loss	1.0000
13:46055758:T:TA	donor_loss	1.0000
13:46055759:T:TC	donor_loss	1.0000
13:46055760:A:AC	donor_gain	1.0000
13:46055761:C:CC	donor_gain	1.0000
13:46055761:C:T	donor_loss	1.0000
13:46055761:CA:C	donor_gain	1.0000
13:46055761:CAT:C	donor_gain	1.0000
13:46055761:CATA:C	donor_gain	1.0000
13:46055761:CATAA:C	donor_gain	1.0000
13:46055845:AGAGA:A	acceptor_gain	1.0000
13:46055846:GAGA:G	acceptor_gain	1.0000
13:46055847:AGA:A	acceptor_gain	1.0000
13:46055848:GA:G	acceptor_gain	1.0000
13:46055850:C:CC	acceptor_gain	1.0000
13:46055851:T:C	acceptor_loss	1.0000
13:46055858:A:T	acceptor_gain	1.0000
13:46058172:CACTT:C	donor_loss	1.0000
13:46058173:ACTTA:A	donor_loss	1.0000
13:46058174:CTTA:C	donor_loss	1.0000
13:46058175:TTA:T	donor_loss	1.0000
13:46058176:TACCA:T	donor_loss	1.0000
13:46058177:A:AC	donor_gain	1.0000
13:46058177:A:AT	donor_loss	1.0000

AlphaMissense

2784 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:46053704:G:C	F394L	0.996
13:46053704:G:T	F394L	0.996
13:46053706:A:G	F394L	0.996
13:46067337:A:C	N224K	0.996
13:46067337:A:T	N224K	0.996
13:46073891:G:C	C191W	0.995
13:46073909:C:A	W185C	0.994
13:46073909:C:G	W185C	0.994
13:46073930:A:C	C178W	0.994
13:46073913:T:A	E184V	0.993
13:46073893:A:G	C191R	0.992
13:46064730:C:A	W238C	0.991
13:46064730:C:G	W238C	0.991
13:46073911:A:G	W185R	0.991
13:46073911:A:T	W185R	0.991
13:46073932:A:G	C178R	0.991
13:46064670:G:C	N258K	0.990
13:46064670:G:T	N258K	0.990
13:46073892:C:T	C191Y	0.990
13:46073931:C:T	C178Y	0.990
13:46064724:C:A	K240N	0.988
13:46064724:C:G	K240N	0.988
13:46073941:A:G	W175R	0.986
13:46073941:A:T	W175R	0.986
13:46058325:A:G	S285P	0.985
13:46058339:C:T	G280E	0.985
13:46064667:A:C	F259L	0.985
13:46064667:A:T	F259L	0.985
13:46064669:A:G	F259L	0.985
13:46064673:C:A	R257S	0.985

dbSNP variants (sampled 300 via entrez): RS1000017871 (13:46078541 A>C), RS1000046731 (13:46054357 T>C), RS1000098859 (13:46106579 CAAAT>C), RS1000108087 (13:46094422 C>T), RS1000228172 (13:46075042 G>A), RS1000291248 (13:46080548 C>T), RS1000398571 (13:46086814 T>G), RS1000416944 (13:46101516 A>C,T), RS1000561965 (13:46066160 C>T), RS1000706404 (13:46075396 C>T), RS1000764332 (13:46084012 C>G,T), RS1000769665 (13:46086630 G>A,T), RS1000802923 (13:46073340 C>A,G), RS1000833551 (13:46091799 A>C,G), RS1000881400 (13:46062785 A>C)

Disease associations

OMIM: gene MIM:603101 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005411_2	Thrombin-activatable fibrinolysis inhibitor activation peptide	1.000000e-27
GCST005412_1	Thrombin-activatable fibrinolysis inhibitor levels	5.000000e-30
GCST005412_7	Thrombin-activatable fibrinolysis inhibitor levels	3.000000e-29

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3419 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 32 (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
CHEMBL398110	UK-396,082	1	32

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M14: Carboxypeptidase A

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 4 [PMID: 19954973]	Inhibition	8.46	pKi
SQ-24,798	Inhibition	8.4	pKi
UK-396,082	Inhibition	8.0	pKi
compound 3 [PMID: 14640538]	Inhibition	6.7	pIC50

Binding affinities (BindingDB)

148 measured of 164 human assays (174 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3577442	IC50	1 nM
(2S)-5-amino-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	2.6 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
CHEMBL3912764	IC50	3 nM
CHEMBL3577439	IC50	4 nM
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(3,3-dimethylbutyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	4.5 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(2S,4R)-5-amino-4-methyl-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	5.1 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S,4S)-5-amino-4-methyl-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	5.4 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S)-6-amino-2-[[(9S,12R)-11-oxo-9-propan-2-yl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]carbamoylamino]hexanoic acid	IC50	6 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
2-[(2R)-1-aminopropan-2-yl]oxy-3-[1-(4-methylcyclohexyl)imidazol-4-yl]propanoic acid	IC50	7 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
5-amino-2-[[1-(3,3-dimethylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	7.5 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S)-6-amino-2-[[(4E,9S,12R)-11-oxo-9-propan-2-yl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(16),4,14,17-tetraen-12-yl]carbamoylamino]hexanoic acid	IC50	7.7 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
(2S)-5-amino-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	7.8 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R,2S)-2-[(2R)-2-(Aminomethyl)butyl]-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	7.9 nM	US-9662310: Cyclopropanecarboxylic acid derivative
2-(2-aminoethoxy)-3-[1-(4-methylcyclohexyl)imidazol-4-yl]propanoic acid	IC50	8.1 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
5-amino-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	8.3 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R,2S)-2-[(2R)-2-(Aminomethyl)butyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	8.3 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R,2S)-2-[(2R)-3-Amino-2-methylpropyl]-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	8.7 nM	US-9662310: Cyclopropanecarboxylic acid derivative
5-amino-2-[[1-(4-ethylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	8.8 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S)-6-amino-2-[[(13S,16R)-15-oxo-13-propan-2-yl-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(20),18,21-trien-16-yl]carbamoylamino]hexanoic acid	IC50	8.8 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
(2S)-3-(6-amino-3-pyridinyl)-2-[[(9S,12R)-11-oxo-9-propan-2-yl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]carbamoylamino]propanoic acid	IC50	9 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
5-amino-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	9.3 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
5-amino-2-[[1-(4-pyridin-4-yloxycyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	9.8 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
4-(aminomethyl)-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]hexanoic acid	IC50	10 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R,2S)-2-(3-Aminopropyl)-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	11 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R,2S)-2-[(2R)-3-Amino-2-methylpropyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	11 nM	US-9662310: Cyclopropanecarboxylic acid derivative
2-[[1-(2-adamantyl)imidazol-4-yl]methyl]-5-aminopentanoic acid	IC50	12 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S)-3-(6-amino-3-pyridinyl)-2-[[(9S,12R)-16-fluoro-11-oxo-9-propan-2-yl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]carbamoylamino]propanoic acid	IC50	12 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
(1R,2S)-2-[	IC50	12 nM	US-9662310: Cyclopropanecarboxylic acid derivative
2-[(2R)-4-Aminobutane-2-yl]-1-[1-(pyridin-2-yl)-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	12 nM	US-9662310: Cyclopropanecarboxylic acid derivative
5-amino-2-[[1-(4-phenoxycyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	13 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R,2S)-2-(3-Aminopropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	13 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R,2S)-2-[(2-Aminomethyl)butyl]-1-(1-phenyl-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	13 nM	US-9662310: Cyclopropanecarboxylic acid derivative
5-amino-2-[[1-(3-ethylcyclobutyl)imidazol-4-yl]methyl]pentanoic acid	IC50	14 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
5-amino-2-[[1-[(2R)-2-bicyclo[2.2.1]heptanyl]imidazol-4-yl]methyl]pentanoic acid	IC50	14 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	14 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R,2S)-2-[(2R)-3-Amino-2-methylpropyl]-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	14 nM	US-9662310: Cyclopropanecarboxylic acid derivative
CHEMBL3577432	IC50	15 nM
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(4-methylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	16 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(5-methoxypyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	16 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R*,2S*)-2-(3-Aminopropyl)-1-(1-isoquinolin-3-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid	IC50	16 nM	US-9662310: Cyclopropanecarboxylic acid derivative
6-amino-2-[[(6R)-5-oxo-1-oxa-4-azacyclotetradec-6-yl]carbamoylamino]hexanoic acid	IC50	17 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
5-amino-2-[[1-(3-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	18 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	18 nM	US-9662310: Cyclopropanecarboxylic acid derivative
5-amino-2-[[1-(4-hydroxy-4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	19 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
5-amino-2-[[1-(4-hydroxycyclohexyl)imidazol-4-yl]methyl]pentanoic acid	IC50	19 nM	US-8609710: Cycloalkyl-substituted imidazole derivative
(2S)-6-amino-2-[[(9S,12R)-9-tert-butyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]carbamoylamino]hexanoic acid	IC50	19 nM	US-9688645: Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(5-fluoropyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	19 nM	US-9662310: Cyclopropanecarboxylic acid derivative
(1R*,2S*)-2-(3-Aminopropyl)-1-[1-(4-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid	IC50	19 nM	US-9662310: Cyclopropanecarboxylic acid derivative
CHEMBL3577336	IC50	19 nM
5-amino-2-[(1-cyclohexylimidazol-4-yl)methyl]pentanoic acid	IC50	21 nM	US-8609710: Cycloalkyl-substituted imidazole derivative

ChEMBL bioactivities

356 potent at pChembl≥5 of 377 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	IC50	0.025	nM	CHEMBL2164450
9.12	Ki	0.75	nM	CHEMBL4878039
9.00	IC50	1	nM	CHEMBL308195
9.00	IC50	1	nM	CHEMBL3577442
9.00	IC50	1	nM	CHEMBL4868605
8.96	IC50	1.1	nM	CHEMBL2164459
8.82	IC50	1.5	nM	ANABAENOPEPTIN F
8.82	IC50	1.5	nM	ANABAENOPEPTIN B
8.82	IC50	1.5	nM	CHEMBL4127473
8.72	IC50	1.9	nM	CHEMBL3577334
8.70	IC50	2	nM	CHEMBL70177
8.70	IC50	2	nM	CHEMBL2164457
8.70	IC50	2	nM	CHEMBL4846664
8.59	IC50	2.6	nM	CHEMBL3640801
8.57	IC50	2.7	nM	CHEMBL68399
8.52	IC50	3	nM	CHEMBL3577425
8.52	IC50	3	nM	CHEMBL3912764
8.52	IC50	3	nM	CHEMBL245787
8.46	Ki	3.5	nM	CHEMBL589645
8.40	IC50	4	nM	CHEMBL68399
8.40	IC50	4	nM	CHEMBL3577435
8.40	IC50	4	nM	CHEMBL3577439
8.40	IC50	4	nM	CHEMBL3577440
8.40	Ki	4	nM	CHEMBL236822
8.40	IC50	4	nM	CHEMBL245787
8.39	IC50	4.1	nM	CHEMBL2164460
8.35	IC50	4.5	nM	CHEMBL6062473
8.30	IC50	5	nM	CHEMBL68399
8.30	IC50	5	nM	CHEMBL245787
8.30	IC50	5	nM	CHEMBL4858095
8.30	IC50	5	nM	CHEMBL4861532
8.29	IC50	5.1	nM	CHEMBL3642855
8.28	IC50	5.3	nM	CHEMBL2164461
8.27	IC50	5.4	nM	CHEMBL3642849
8.26	IC50	5.5	nM	CHEMBL2164463
8.24	Ki	5.7	nM	CHEMBL589646
8.24	Ki	5.8	nM	CHEMBL590857
8.22	IC50	6	nM	CHEMBL149680
8.22	IC50	6	nM	CHEMBL4878039
8.22	IC50	6	nM	CHEMBL5911745
8.17	Ki	6.7	nM	CHEMBL609577
8.15	IC50	7	nM	CHEMBL3577433
8.15	IC50	7	nM	CHEMBL3577425
8.15	IC50	7	nM	CHEMBL3640803
8.15	IC50	7	nM	CHEMBL4853133
8.12	IC50	7.5	nM	CHEMBL3642847
8.12	Ki	7.5	nM	CHEMBL601926
8.11	IC50	7.8	nM	CHEMBL3640801
8.11	IC50	7.7	nM	CHEMBL5819059
8.10	IC50	8	nM	CHEMBL3235132

PubChem BioAssay actives

248 with measured affinity, of 337 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
3-(6-amino-3-pyridinyl)-2-[[[3-(6-amino-3-pyridinyl)-2-carboxypropyl]diselanyl]methyl]propanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	<0.0001	uM
3-(6-amino-5-chloro-3-pyridinyl)-2-[[[3-(6-amino-5-chloro-3-pyridinyl)-2-carboxypropyl]diselanyl]methyl]propanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	<0.0001	uM
(3S)-3-(4-aminobutyl)-1-[[4-fluoro-2-(3-methylimidazol-4-yl)phenyl]methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ki	0.0008	uM
(2S)-3-(6-amino-3-pyridinyl)-2-[[(2R)-3-cyclohexyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]propanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0010	uM
(3S)-3-(4-aminobutyl)-1-[[4-fluoro-2-(4-methylphenyl)phenyl]methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0010	uM
3-[(1R,3S)-3-aminocyclopentyl]-2-[1-(3,3-dimethylbutyl)imidazol-4-yl]propanoic acid	208844: Inhibitory potency against human TAFIa (thrombin-activatable fibrinolysis inhibitor)	ic50	0.0010	uM
7-amino-2-(propanoylselanylmethyl)heptanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	0.0011	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3-benzyl-9-[2-(4-hydroxyphenyl)ethyl]-6,7-dimethyl-2,5,8,11,14-pentaoxo-12-propan-2-yl-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0015	uM
2-[(6-amino-5-chloro-3-pyridinyl)methyl]-3-propanoylselanylpropanoic acid	1497827: Inhibition of human plasma activated thrombin-activatable fibrinolysis inhibitor after 10 mins in presence of DTT	ic50	0.0015	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3-benzyl-12-[(2S)-butan-2-yl]-9-[2-(4-hydroxyphenyl)ethyl]-6,7-dimethyl-2,5,8,11,14-pentaoxo-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0015	uM
(2S)-6-amino-2-[[(3S,6S,9S,12S,15R)-3-benzyl-9-[2-(4-hydroxyphenyl)ethyl]-6,7-dimethyl-2,5,8,11,14-pentaoxo-12-propan-2-yl-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]hexanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0019	uM
3-(4-aminobutyl)-4-hydroxy-4-oxo-1-[(2-pyridin-3-ylphenyl)methyl]-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0020	uM
3-(6-amino-3-pyridinyl)-2-[1-(4-methylpentyl)imidazol-4-yl]propanoic acid	208844: Inhibitory potency against human TAFIa (thrombin-activatable fibrinolysis inhibitor)	ic50	0.0020	uM
7-amino-2-[[(7-amino-2-carboxyheptyl)diselanyl]methyl]heptanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	0.0020	uM
3-(6-amino-3-pyridinyl)-2-[1-(3-methylbutyl)imidazol-4-yl]propanoic acid	48496: In vitro inhibition of purified Carboxypeptidase B (CPB) by clot lysis assay in human plasma	ic50	0.0027	uM
2-[3-(diaminomethylideneamino)phenyl]-3-sulfanylpropanoic acid	305878: Inhibition of human activated thrombin activatable fibrinolysis inhibitor	ic50	0.0030	uM
(2S)-6-amino-2-[[(2R)-3-cyclohexyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]hexanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0030	uM
(2S)-6-amino-2-[[(2S)-3-cyclohexyl-1-oxo-1-[[(2S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]amino]propan-2-yl]carbamoylamino]hexanoic acid	1322397: Inhibition of activated human plasma TAFI incubated for 15 mins by chromogenic assay	ic50	0.0030	uM
(2S)-2-(2-aminoethoxy)-3-(1-phenylimidazol-4-yl)propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0035	uM
(2S)-6-amino-2-[[3-cyclopentyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]hexanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0040	uM
(2R)-3-(2-aminoethylsulfanyl)-2-[[(2R)-3-cyclohexyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]propanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0040	uM
(2S)-2-[[(2R)-3-cyclohexyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0040	uM
5-(diaminomethylideneamino)-2-(sulfanylmethyl)pentanoic acid	304051: Inhibition of human TAFIa	ki	0.0040	uM
7-amino-2-(4-phenylbutanoylselanylmethyl)heptanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	0.0041	uM
(3S)-3-(4-aminobutyl)-4-hydroxy-1-[[2-(6-methoxy-3-pyridinyl)phenyl]methyl]-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0050	uM
(3S)-3-(4-aminobutyl)-1-[(4-fluoro-2-pyrimidin-5-ylphenyl)methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0050	uM
7-amino-2-(3-phenylpropanoylselanylmethyl)heptanoic acid	699460: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis in presence of dithiothreitol	ic50	0.0053	uM
(2S)-7-amino-2-[[hydroxy-[(1R)-2-methyl-1-(3-phenylpropanoylamino)propyl]phosphoryl]methyl]heptanoic acid	699463: Inhibition of human activated TAFI using Hip-Arg as substrate incubated for 10 mins prior to substrate addition measured after 30 mins by spectrophotometric analysis	ic50	0.0055	uM
(2S)-2-(2-aminoethoxy)-3-[1-(4-tert-butylphenyl)imidazol-4-yl]propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0057	uM
(2S)-2-[(2R)-1-aminopropan-2-yl]oxy-3-(1-pyridin-2-ylimidazol-4-yl)propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0058	uM
3-(6-amino-3-pyridinyl)-2-(1-butylimidazol-4-yl)propanoic acid	48496: In vitro inhibition of purified Carboxypeptidase B (CPB) by clot lysis assay in human plasma	ic50	0.0060	uM
(2S)-2-(2-aminoethoxy)-3-(1-propylimidazol-4-yl)propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0067	uM
(2S)-6-amino-2-[[(2R)-3-cyclopropyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]hexanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0070	uM
3-(4-aminobutyl)-4-hydroxy-4-oxo-1-[(2-pyrimidin-5-ylphenyl)methyl]-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0070	uM
(2S)-2-[(2R)-1-aminopropan-2-yl]oxy-3-(1-phenylimidazol-4-yl)propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0075	uM
(3S)-3-(4-aminobutyl)-1-[[4-fluoro-2-(4-methoxyphenyl)phenyl]methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0080	uM
(3S)-3-(4-aminobutyl)-1-[[2-(3,4-dimethoxyphenyl)-4-fluorophenyl]methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0080	uM
(5R)-5-(3-aminopropyl)-1-propyl-6,7-dihydro-4H-benzimidazole-5-carboxylic acid	1129020: Inhibition of human TAF1a using hippuryl-L-arginine/hippuryl-L-lysine as substrate by liquid chromatographic analysis	ic50	0.0080	uM
2-(4,4-diaminobut-3-enylsulfanylmethyl)-3-sulfanylpropanoic acid	48496: In vitro inhibition of purified Carboxypeptidase B (CPB) by clot lysis assay in human plasma	ic50	0.0082	uM
(2S)-2-(2-aminoethoxy)-3-[1-(2-cyclohexylethyl)imidazol-4-yl]propanoic acid	452510: Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	ki	0.0082	uM
(2S)-6-amino-2-[[(2R)-3-cyclobutyl-1-oxo-1-[(4,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl)amino]propan-2-yl]carbamoylamino]hexanoic acid	1227127: Inhibition of human activated TAFI incubated for 15 mins by microtiter plate reader based assay	ic50	0.0090	uM
(3S)-3-(4-aminobutyl)-4-hydroxy-1-[(4-hydroxy-2-phenylphenyl)methyl]-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0090	uM
(3S)-3-(4-aminobutyl)-4-hydroxy-1-[[2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]phenyl]methyl]-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0090	uM
(2S)-5-amino-2-[(1-propylimidazol-4-yl)methyl]pentanoic acid	304051: Inhibition of human TAFIa	ki	0.0100	uM
(3S)-3-(4-aminobutyl)-1-[[4-chloro-2-(4-chlorophenyl)phenyl]methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0100	uM
(2S)-6-amino-2-[[(8R,11S)-2,9-dioxo-11-propan-2-yl-13-thia-3,10,15-triazabicyclo[10.2.1]pentadeca-1(14),12(15)-dien-8-yl]carbamoylamino]hexanoic acid	1677492: Inhibition of TAFIalpha in human plasma incubated for 15 mins by chromogenic assay	ic50	0.0100	uM
2-[2-chloro-5-(diaminomethylideneamino)phenyl]-3-sulfanylpropanoic acid	305878: Inhibition of human activated thrombin activatable fibrinolysis inhibitor	ic50	0.0110	uM
(3S)-3-(4-aminobutyl)-1-[(4-fluoro-2-phenylphenyl)methyl]-4-hydroxy-4-oxo-1,4lambda5-azaphosphinane-3-carboxylic acid	1775820: Inhibition of recombinant human activated TAFI incubated for 45 mins using hippuryl-arginine as substrate by spectrophotometry	ic50	0.0110	uM
(2S)-6-amino-2-[[(2S)-3-cyclohexyl-1-oxo-1-[[(1R,2S,4R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]amino]propan-2-yl]sulfamoylamino]hexanoic acid	1322397: Inhibition of activated human plasma TAFI incubated for 15 mins by chromogenic assay	ic50	0.0120	uM
3-(6-amino-5-methyl-3-pyridinyl)-2-[1-(4-methylpentyl)imidazol-4-yl]propanoic acid	208844: Inhibitory potency against human TAFIa (thrombin-activatable fibrinolysis inhibitor)	ic50	0.0120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	7
Cyclosporine	decreases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
Tetrachlorodibenzodioxin	decreases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
ethinyl estradiol-desogestrel combination	increases activity	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
(+)-JQ1 compound	decreases expression	1
Orlistat	decreases expression	1
Glyphosate	increases expression	1
Air Pollutants	decreases expression	1
Azathioprine	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069123	Binding	Inhibition of active form of human recombinant TAFI assessed as substrate turnover every 15 seconds for 30 mins	Oxygenated analogues of UK-396082 as inhibitors of activated thrombin activatable fibrinolysis inhibitor. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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