CPB1

Summary

CPB1 (carboxypeptidase B1, HGNC:2299) is a protein-coding gene on chromosome 3q24, encoding Carboxypeptidase B (P15086).

Three different procarboxypeptidases A and two different procarboxypeptidases B have been isolated. The B1 and B2 forms differ from each other mainly in isoelectric point. Carboxypeptidase B1 is a highly tissue-specific protein and is a useful serum marker for acute pancreatitis and dysfunction of pancreatic transplants. It is not elevated in pancreatic carcinoma.

Source: NCBI Gene 1360 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2299
Approved symbol	CPB1
Name	carboxypeptidase B1
Location	3q24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153002
Ensembl biotype	protein_coding
OMIM	114852
Entrez	1360

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000282957, ENST00000462345, ENST00000465718, ENST00000468341, ENST00000473621, ENST00000476847, ENST00000484877, ENST00000491148, ENST00000494888, ENST00000498639, ENST00000968620

RefSeq mRNA: 1 — MANE Select: NM_001871 NM_001871

CCDS: CCDS33874

Canonical transcript exons

ENST00000282957 — 11 exons

Exon	Start	End
ENSE00001870122	148827811	148827894
ENSE00003462549	148859815	148860187
ENSE00003514753	148857457	148857541
ENSE00003521953	148841823	148841924
ENSE00003539028	148840874	148840975
ENSE00003539691	148834498	148834622
ENSE00003628725	148840686	148840785
ENSE00003888766	148845424	148845626
ENSE00003890543	148844677	148844767
ENSE00003890545	148844478	148844588
ENSE00003890895	148828002	148828077

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 153.0149 / max 270771.4165, expressed in 190 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39073	150.1434	30
39101	1.0985	54
39072	0.9085	10
39074	0.2170	4
39067	0.1780	73
39068	0.1325	31
39075	0.0686	3
39100	0.0572	22
202965	0.0426	2
202964	0.0396	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.98	gold quality
islet of Langerhans	UBERON:0000006	99.66	gold quality
pancreas	UBERON:0001264	99.61	gold quality
type B pancreatic cell	CL:0000169	98.47	gold quality
right adrenal gland cortex	UBERON:0035827	97.93	gold quality
left adrenal gland cortex	UBERON:0035825	97.91	gold quality
right adrenal gland	UBERON:0001233	97.70	gold quality
left adrenal gland	UBERON:0001234	97.55	gold quality
adrenal cortex	UBERON:0001235	97.55	gold quality
adrenal gland	UBERON:0002369	95.83	gold quality
epithelial cell of pancreas	CL:0000083	93.33	gold quality
adrenal tissue	UBERON:0018303	93.33	gold quality
spleen	UBERON:0002106	84.48	gold quality
omental fat pad	UBERON:0010414	82.77	gold quality
peritoneum	UBERON:0002358	82.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.42	gold quality
body of stomach	UBERON:0001161	78.85	gold quality
ectocervix	UBERON:0012249	77.67	gold quality
right coronary artery	UBERON:0001625	76.83	gold quality
right lobe of liver	UBERON:0001114	76.26	gold quality
left uterine tube	UBERON:0001303	75.72	gold quality
mammary duct	UBERON:0001765	75.54	gold quality
epithelium of mammary gland	UBERON:0003244	74.71	gold quality
metanephros cortex	UBERON:0010533	74.33	gold quality
stomach	UBERON:0000945	74.12	gold quality
lower esophagus mucosa	UBERON:0035834	74.12	gold quality
endocervix	UBERON:0000458	73.67	gold quality
descending thoracic aorta	UBERON:0002345	73.36	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	31199.69
E-HCAD-23	yes	15680.67
E-MTAB-5061	yes	20.51
E-ENAD-27	yes	7.15
E-HCAD-31	yes	5.24
E-GEOD-81608	yes	4.45
E-GEOD-83139	no	3.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CPB1, 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-3646	100.00	73.56	5283
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-4529-5P	96.74	65.77	569

Literature-anchored findings (GeneRIF, showing 6)

• TAFI and CPB modulate the plasminogen system both in the matrix and on the cell surface, thus leading to the inhibition of endothelial cell movement and tube formation. (PMID:17673703)
• The structure of the tick carboxypeptidase inhibitor (TCI) and its backbone dynamics, free and in complex with human carboxypeptidase B, have been determined by NMR spectroscopy. (PMID:18558717)
• These findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-kappaB pathway and changes in cell survival and cytoskeleton. (PMID:25903579)
• This study showed that CPA2 and CPB1 variants are not associated with chronic pancreatitis. (PMID:26316592)
• study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development. (PMID:29669919)
• Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis. (PMID:34817877)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpb1	ENSDARG00000045442
mus_musculus	Cpb1	ENSMUSG00000011463
rattus_norvegicus	Cpb1	ENSRNOG00000030904
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	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

Paralogs (8): CPB2 (ENSG00000080618), CPA1 (ENSG00000091704), CPA4 (ENSG00000128510), CPO (ENSG00000144410), CPA2 (ENSG00000158516), CPA5 (ENSG00000158525), CPA3 (ENSG00000163751), CPA6 (ENSG00000165078)

Protein

Protein identifiers

Carboxypeptidase B — P15086 (reviewed: P15086)

Alternative names: Pancreas-specific protein

All UniProt accessions (4): P15086, C9J5C4, C9JUX7, C9JXS3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Zymogen granule lumen.

Tissue specificity. Pancreas.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

RefSeq proteins (1): NP_001862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR003146	M14A_act_pep	Domain
IPR034253	CPB_M14_CPD	Domain
IPR036990	M14A-like_propep	Homologous_superfamily
IPR057246	CARBOXYPEPT_ZN_1	Binding_site
IPR057247	CARBOXYPEPT_ZN_2	Binding_site

Pfam: PF00246, PF02244

Enzyme classification (BRENDA):

• EC 3.4.17.2 — carboxypeptidase B (BRENDA: 26 organisms, 70 substrates, 92 inhibitors, 41 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
HIPPURYL-L-ARG	0.05–28	13
BENZOYL-GLY-ARG	0.1–8	4
HIPPURYL-ARG	0.277–0.54	4
BENZOYL-GLY-GLY-PHE	24–40	2
BENZOYL-GLY-GLYCYLPHENYLLACTIC ACID	3–80	2
CARBOBENZOXY-GLY-PHE	80–100	2
FURYLACRYLOYLALANYLLYSINE	0.07–0.11	2
HIPPURYL-LYS	2.63–3.55	2
3-(2-FURYL)ACRYLOYL-L-ALA-L-ARG	0.012	1
BENZOYL-GLY-L-ARG	0.32	1
BIOTIN-(EPSILON-AMINOCAPROIC ACID)2-GLMVGGVVR	0.008	1
FURYLACRYLOYL-L-ALANYL-L-ARGININE	0.1	1
FURYLACRYLOYLALANYLARGININE	0.12	1
N-(4-METHOXYPHENYLAZOFORMYL)-ARG	0.06	1
N-(PHENYLCARBONYL)GLYCYL-L-ARGININE	0.6	1

UniProt features (59 total): helix 18, strand 17, binding site 8, sequence conflict 4, disulfide bond 3, turn 3, signal peptide 1, propeptide 1, sequence variant 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1KWM	X-RAY DIFFRACTION	1.6
1ZLI	X-RAY DIFFRACTION	2.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15086-F1	95.71	0.95

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 (1): 378 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 304; 305–306; 356; 176–179; 176; 179; 234; 251–252

Disulfide bonds (3): 173–186, 245–268, 259–273

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-1266738	Developmental Biology
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 96 (showing top): chr3q24, GOMF_METALLOPEPTIDASE_ACTIVITY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN, MODULE_492, SABATES_COLORECTAL_ADENOMA_DN, TURASHVILI_BREAST_CARCINOMA_DUCTAL_VS_LOBULAR_UP, XU_GH1_EXOGENOUS_TARGETS_DN, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_EXOPEPTIDASE_ACTIVITY

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (8): carboxypeptidase activity (GO:0004180), metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasmic vesicle (GO:0031410), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Peptide hormone metabolism	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Metabolism of proteins	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
exopeptidase activity	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPB1	PLG	P00747	851
CPB1	CPE	P16870	804
CPB1	CPN1	P15169	783
CPB1	CPN2	P22792	718
CPB1	CTRB1	P17538	677
CPB1	CTRB2	Q6GPI1	667
CPB1	SERPINI2	O75830	654
CPB1	PLAT	P00750	615
CPB1	CELA2A	P08217	591
CPB1	ENO1	P06733	586
CPB1	PRSS1	P07477	577
CPB1	THBD	P07204	577
CPB1	RNPEP	Q9H4A4	552
CPB1	CELA3A	P09093	528
CPB1	PROC	P04070	524

IntAct

4 interactions, top by confidence:

A	B	Type	Score
APP	CPB1	psi-mi:“MI:0915”(physical association)	0.560

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: A0A1S4F020, A6XGK3, B6H233, B6Q972, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4DL57, O02350, P00730, P00731, P00732, P04069, P09954, P09955, P15085, P15086, P18143, P19222, P19223, P29068, P38836, P42788, P48052, P55261, Q0C9B4, Q0II73, Q29NC4, Q3T905, Q504N0, Q5U901, Q7TPZ8, Q8IVL8, Q8N4T0, Q9VL86, A1CSU3, A1DGH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	7
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1951 predictions. Top by Δscore:

Variant	Effect	Δscore
3:148827985:A:AG	acceptor_gain	1.0000
3:148827993:A:AG	acceptor_gain	1.0000
3:148827994:T:G	acceptor_gain	1.0000
3:148827997:T:G	acceptor_gain	1.0000
3:148828000:A:AG	acceptor_gain	1.0000
3:148828001:G:GG	acceptor_gain	1.0000
3:148828076:AG:A	donor_gain	1.0000
3:148828077:GG:G	donor_gain	1.0000
3:148828078:G:GG	donor_gain	1.0000
3:148834619:ACAAG:A	donor_loss	1.0000
3:148834620:CAA:C	donor_gain	1.0000
3:148834620:CAAG:C	donor_loss	1.0000
3:148834621:AA:A	donor_gain	1.0000
3:148834622:AGTA:A	donor_loss	1.0000
3:148834623:G:GG	donor_gain	1.0000
3:148834623:G:T	donor_loss	1.0000
3:148834624:TAAGT:T	donor_loss	1.0000
3:148841920:GAGAG:G	donor_gain	1.0000
3:148844463:A:AG	acceptor_gain	1.0000
3:148844464:T:G	acceptor_gain	1.0000
3:148844465:A:AG	acceptor_gain	1.0000
3:148844471:C:G	acceptor_gain	1.0000
3:148844476:AGGC:A	acceptor_loss	1.0000
3:148844477:G:A	acceptor_loss	1.0000
3:148844584:CCAAG:C	donor_loss	1.0000
3:148844585:CAAGG:C	donor_loss	1.0000
3:148844586:AAGGT:A	donor_loss	1.0000
3:148844587:AG:A	donor_loss	1.0000
3:148844588:GGTAT:G	donor_loss	1.0000
3:148844590:T:A	donor_loss	1.0000

AlphaMissense

2723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:148841886:T:A	W180R	0.997
3:148841886:T:C	W180R	0.997
3:148841888:G:C	W180C	0.997
3:148841888:G:T	W180C	0.997
3:148844744:G:C	R252T	0.997
3:148859907:T:C	F387L	0.997
3:148859909:T:A	F387L	0.997
3:148859909:T:G	F387L	0.997
3:148841884:A:T	E179V	0.996
3:148844744:G:T	R252I	0.996
3:148844745:A:C	R252S	0.996
3:148844745:A:T	R252S	0.996
3:148844748:T:A	N253K	0.996
3:148844748:T:G	N253K	0.996
3:148841874:C:G	H176D	0.995
3:148844735:A:G	D249G	0.995
3:148841906:C:G	C186W	0.994
3:148844558:T:A	N219K	0.994
3:148844558:T:G	N219K	0.994
3:148845555:C:G	H304D	0.994
3:148859843:G:C	W365C	0.993
3:148859843:G:T	W365C	0.993
3:148841867:T:G	C173W	0.992
3:148841904:T:C	C186R	0.992
3:148841905:G:A	C186Y	0.992
3:148844734:G:C	D249H	0.992
3:148844735:A:T	D249V	0.992
3:148844736:C:A	D249E	0.992
3:148844736:C:G	D249E	0.992
3:148845466:G:A	G274E	0.992

dbSNP variants (sampled 300 via entrez): RS1000010665 (3:148836728 A>G,T), RS1000049329 (3:148826122 T>C), RS1000051883 (3:148829654 C>G), RS1000078965 (3:148833380 A>G), RS1000195533 (3:148855232 G>T), RS1000347432 (3:148858342 G>A), RS1000381019 (3:148830288 G>A), RS1000401310 (3:148858094 G>A), RS1000736284 (3:148859314 G>T), RS1000861997 (3:148843497 T>A,C), RS1000875100 (3:148852834 C>G), RS1000930207 (3:148856659 G>A), RS1000946346 (3:148850459 A>G,T), RS1001001611 (3:148850011 C>T), RS1001091780 (3:148845760 T>C)

Disease associations

OMIM: gene MIM:114852 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002831_6	Lead levels in blood	2.000000e-06
GCST006585_983	Blood protein levels	1.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2552 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 14640538]	Inhibition	8.09	pIC50
compound 4 [PMID: 19954973]	Inhibition	7.57	pKi

Binding affinities (BindingDB)

17 measured of 17 human assays (17 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(6-amino-3-pyridinyl)-2-[1-(4,4-dimethylcyclohexyl)imidazol-4-yl]propanoic acid	IC50	3 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[[1-(2,2-diphenylacetyl)piperidin-3-yl]methyl]imidazol-4-yl]propanoic acid	IC50	11 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[2-[1-(2,2-diphenylacetyl)piperidin-4-yl]ethyl]imidazol-4-yl]propanoic acid	IC50	12 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[(1-benzoylpiperidin-2-yl)methyl]imidazol-4-yl]propanoic acid	IC50	12 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[4-(phenylcarbamoylamino)phenyl]imidazol-4-yl]propanoic acid	IC50	15 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-(1-cyclopentylimidazol-4-yl)propanoic acid	IC50	16 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[2-[1-(3-phenylpropanoyl)piperidin-4-yl]ethyl]imidazol-4-yl]propanoic acid	IC50	21 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[2-(benzhydrylamino)-2-oxoethyl]imidazol-4-yl]propanoic acid	IC50	23 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-(1-cyclohexylimidazol-4-yl)propanoic acid	IC50	30 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[2-[1-(3-phenylpropanoyl)piperidin-3-yl]ethyl]imidazol-4-yl]propanoic acid	IC50	38 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[4-(propylcarbamoylamino)phenyl]imidazol-4-yl]propanoic acid	IC50	49 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-(2-oxo-1-phenylpyrrolidin-3-yl)imidazol-4-yl]propanoic acid	IC50	439 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-(1-prop-2-ynylimidazol-4-yl)propanoic acid	IC50	870 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[(5-chloro-1-benzothiophen-3-yl)methyl]imidazol-4-yl]propanoic acid	IC50	1110 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-(1-piperidin-4-ylimidazol-4-yl)propanoic acid	IC50	1130 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[[3-(4-fluorophenoxy)phenyl]methyl]imidazol-4-yl]propanoic acid	IC50	1440 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors
3-(6-amino-3-pyridinyl)-2-[1-[[4-(trifluoromethoxy)phenyl]methyl]imidazol-4-yl]propanoic acid	IC50	10500 nM	US-8710232: Imidazole derivatives used as TAFIa inhibitors

ChEMBL bioactivities

58 potent at pChembl≥5 of 81 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	Ki	0.12	nM	CHEMBL4460840
9.00	IC50	1	nM	CHEMBL302054
9.00	IC50	1	nM	CHEMBL308195
9.00	IC50	1	nM	CHEMBL66512
9.00	IC50	1	nM	CHEMBL3577425
8.52	IC50	3	nM	CHEMBL3694281
8.40	IC50	4	nM	CHEMBL70177
8.40	IC50	4	nM	CHEMBL68399
7.96	IC50	11	nM	CHEMBL3694275
7.92	IC50	12	nM	CHEMBL3694272
7.92	IC50	12	nM	CHEMBL3694273
7.82	IC50	15	nM	CHEMBL3694271
7.80	IC50	16	nM	CHEMBL3694267
7.70	IC50	20	nM	CHEMBL303664
7.68	IC50	21	nM	CHEMBL3694276
7.64	IC50	23	nM	CHEMBL3694270
7.57	Ki	27	nM	CHEMBL589645
7.57	Ki	27	nM	CHEMBL594359
7.52	IC50	30	nM	CHEMBL3694266
7.42	IC50	38	nM	CHEMBL3694274
7.31	IC50	49	nM	CHEMBL3694282
7.31	Ki	49	nM	CHEMBL589646
7.16	IC50	70	nM	CHEMBL302067
6.82	IC50	150	nM	CHEMBL302817
6.80	IC50	160	nM	CHEMBL66508
6.72	IC50	190	nM	CHEMBL3577333
6.69	Ki	206	nM	UK-396,082
6.62	Ki	238	nM	CHEMBL609577
6.62	Ki	240	nM	CHEMBL601926
6.58	Ki	265	nM	CHEMBL590857
6.44	IC50	360	nM	LYSIANADIOIC ACID
6.44	Ki	360	nM	CHEMBL590859
6.36	IC50	439	nM	CHEMBL3694269
6.22	IC50	600	nM	CHEMBL69883
6.06	IC50	870	nM	CHEMBL3694280
5.97	Ki	1060	nM	CHEMBL516131
5.96	IC50	1110	nM	CHEMBL3694278
5.96	Ki	1100	nM	CHEMBL560871
5.95	IC50	1130	nM	CHEMBL3694268
5.94	Ki	1160	nM	CHEMBL236547
5.92	Ki	1200	nM	CHEMBL552336
5.84	IC50	1440	nM	CHEMBL3694279
5.82	IC50	1500	nM	CHEMBL69955
5.57	Ki	2720	nM	CHEMBL606237
5.52	Ki	3000	nM	CHEMBL515968
5.43	IC50	3700	nM	CHEMBL65910
5.41	Ki	3900	nM	CHEMBL515809
5.35	Ki	4500	nM	CHEMBL551268
5.31	Ki	4900	nM	CHEMBL563744
5.28	Ki	5300	nM	CHEMBL4878039

PubChem BioAssay actives

42 with measured affinity, of 85 total; 42 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
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-2-phenylethyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1614548: Inhibition of human CPB1 using AAFA as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	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	1227134: Inhibition of CBP (unknown origin)	ic50	0.0010	uM
3-[(1R,3S)-3-aminocyclopentyl]-2-[1-(3,3-dimethylbutyl)imidazol-4-yl]propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0010	uM
3-(6-amino-5-methyl-3-pyridinyl)-2-[1-(4-methylpentyl)imidazol-4-yl]propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0010	uM
3-(6-amino-5-methyl-3-pyridinyl)-2-[1-(3-methylbutyl)imidazol-4-yl]propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0010	uM
3-(6-amino-3-pyridinyl)-2-[1-(4-methylpentyl)imidazol-4-yl]propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0040	uM
3-(6-amino-3-pyridinyl)-2-[1-(3-methylbutyl)imidazol-4-yl]propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0040	uM
3-(6-amino-5-methyl-3-pyridinyl)-2-(1H-imidazol-5-yl)propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0200	uM
(2S)-2-(2-aminoethoxy)-3-(1-phenylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.0270	uM
(2S)-2-(2-aminoethoxy)-3-[1-(2-cyclohexylethyl)imidazol-4-yl]propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.0270	uM
(2S)-2-(2-aminoethoxy)-3-[1-(4-tert-butylphenyl)imidazol-4-yl]propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.0490	uM
3-(6-amino-3-pyridinyl)-2-(1H-imidazol-5-yl)propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.0700	uM
3-[(1R,3S)-3-aminocyclopentyl]-2-(1-ethylimidazol-4-yl)propanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.1500	uM
6-amino-2-[1-(3-methylbutyl)imidazol-4-yl]hexanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.1600	uM
(2S)-6-amino-2-[[(2R)-1-(3-methylbutylamino)-1-oxo-6-(phenylmethoxycarbonylamino)hexan-2-yl]carbamoylamino]hexanoic acid	1227134: Inhibition of CBP (unknown origin)	ic50	0.1900	uM
(2S)-5-amino-2-[(1-propylimidazol-4-yl)methyl]pentanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.2060	uM
(2S)-2-(2-aminoethoxy)-3-(1-propylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.2380	uM
(2S)-2-[(2R)-1-aminopropan-2-yl]oxy-3-(1-phenylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.2400	uM
(2S)-2-[(2R)-1-aminopropan-2-yl]oxy-3-(1-pyridin-2-ylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.2650	uM
(2Z)-2-[3-(diaminomethylideneamino)propylidene]butanedioic acid	314211: Inhibition of carboxypeptidase B	ic50	0.3600	uM
2-(2-aminoethoxy)-3-(1-butylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	0.3600	uM
6-amino-2-(1H-imidazol-5-yl)-5,5-dimethylhexanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	0.6000	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-(4-nitrophenyl)-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	1.0600	uM
2-[2-(diaminomethylideneamino)ethylsulfanyl]butanedioic acid	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	1.1000	uM
(2S)-2-(2-aminoethylamino)-3-(1-propylimidazol-4-yl)propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	1.1600	uM
N-(3-chlorophenyl)-4-[[5-[(3-methoxyphenyl)methylsulfanyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-thiazol-2-amine	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	1.2000	uM
6-amino-2-(1H-imidazol-5-yl)-5-methylhexanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	1.5000	uM
2-(2-aminoethoxy)-3-[1-(2-methylphenyl)imidazol-4-yl]propanoic acid	452511: Inhibition of human pancreatic carboxypeptidase B	ki	2.7200	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-(4-methoxyphenyl)-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	3.0000	uM
6-amino-2-(1H-imidazol-5-yl)hexanoic acid	48495: Inhibition of human carboxypeptidase B (CPB)	ic50	3.7000	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-[4-(trifluoromethyl)phenyl]-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	3.9000	uM
N-benzyl-N-(4-phenyl-1,3-thiazol-2-yl)cyclopropanecarboxamide	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	4.5000	uM
methyl 2-[[4-benzyl-5-(2-hydroxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]acetate	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	4.9000	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	1775822: Inhibition of recombinant human pancreatic CPB incubated for 25 mins using hippuryl-arginine as substrate by spectrophotometry	ki	5.3000	uM
N-[[di(propan-2-yl)amino]-[(2S,3R)-3-thiophen-2-yl-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	7.2000	uM
propan-2-yl 2-[[4-benzyl-5-(2-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]acetate	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	7.4000	uM
1-(4-chlorophenyl)-2-[[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]ethanone	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	7.5000	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-(4-methylphenyl)-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	9.1000	uM
2-[[4-(furan-2-ylmethyl)-5-(4-hydroxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]-1-thiophen-2-ylethanone	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	9.1000	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-thiophen-3-yl-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	9.2000	uM
N-[[di(propan-2-yl)amino]-[(2S,3S)-3-pyridin-4-yl-2-trimethylsilyloxiran-2-yl]phosphinothioyl]-N-propan-2-ylpropan-2-amine	382338: Inhibition of human carboxypeptidase B	ki	9.7000	uM
2-benzylbutanedioic acid	429518: Inhibition of human recombinant carboxypeptidase B expressed in Pichia pastoris system	ki	10.0000	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases expression	2
kojic acid	decreases expression	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Phthalic Acids	decreases methylation	1
Silicon Dioxide	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024278	Binding	Inhibition of human recombinant carboxypeptidase B expressed in Saccharomyces cerevisiae by microtiter plate method	Cyclobutane-containing peptides: evaluation as novel metallocarboxypeptidase inhibitors and modelling of their mode of action. — Bioorg Med Chem

Clinical trials (associated diseases)

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