CMA1

Summary

CMA1 (chymase 1, HGNC:2097) is a protein-coding gene on chromosome 14q12, encoding Chymase (P23946). Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.

This gene encodes a chymotryptic serine proteinase that belongs to the peptidase family S1. It is expressed in mast cells and is thought to function in the degradation of the extracellular matrix, the regulation of submucosal gland secretion, and the generation of vasoactive peptides. In the heart and blood vessels, this protein, rather than angiotensin converting enzyme, is largely responsible for converting angiotensin I to the vasoactive peptide angiotensin II. Alternative splicing results in multiple variants.

Source: NCBI Gene 1215 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2097
Approved symbol	CMA1
Name	chymase 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000092009
Ensembl biotype	protein_coding
OMIM	118938
Entrez	1215

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000206446, ENST00000250378

RefSeq mRNA: 2 — MANE Select: NM_001836 NM_001308083, NM_001836

CCDS: CCDS76666, CCDS9630

Canonical transcript exons

ENST00000250378 — 5 exons

Exon	Start	End
ENSE00000654524	24506028	24506282
ENSE00001144738	24507356	24507506
ENSE00001816406	24505353	24505659
ENSE00003460379	24508178	24508265
ENSE00003633345	24506469	24506604

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 97.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.2722 / max 2443.2769, expressed in 60 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142614	5.2378	59
142613	0.0269	8
142612	0.0075	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.77	gold quality
skin of hip	UBERON:0001554	77.35	gold quality
gall bladder	UBERON:0002110	77.35	gold quality
rectum	UBERON:0001052	76.24	gold quality
skin of leg	UBERON:0001511	74.61	gold quality
zone of skin	UBERON:0000014	73.30	gold quality
skin of abdomen	UBERON:0001416	73.19	gold quality
subcutaneous adipose tissue	UBERON:0002190	72.60	gold quality
colonic epithelium	UBERON:0000397	72.47	gold quality
mucosa of transverse colon	UBERON:0004991	72.03	gold quality
upper arm skin	UBERON:0004263	71.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.44	gold quality
lower esophagus	UBERON:0013473	70.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.12	gold quality
upper leg skin	UBERON:0004262	70.01	gold quality
minor salivary gland	UBERON:0001830	67.75	gold quality
adipose tissue	UBERON:0001013	67.73	gold quality
connective tissue	UBERON:0002384	67.00	gold quality
vermiform appendix	UBERON:0001154	66.59	gold quality
pancreatic ductal cell	CL:0002079	66.15	silver quality
smooth muscle tissue	UBERON:0001135	65.35	gold quality
mucosa of stomach	UBERON:0001199	65.06	gold quality
mouth mucosa	UBERON:0003729	65.06	gold quality
saliva-secreting gland	UBERON:0001044	64.58	gold quality
apex of heart	UBERON:0002098	64.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.83	gold quality
omental fat pad	UBERON:0010414	63.39	gold quality
peritoneum	UBERON:0002358	63.33	gold quality
esophagus	UBERON:0001043	63.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	63.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.90
E-CURD-46	yes	5.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, MITF

miRNA regulators (miRDB)

13 targeting CMA1, 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-6755-5P	99.95	65.59	464
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958

Literature-anchored findings (GeneRIF, showing 40)

• The S1 primary specificity pocket defines substrate specificity of chymases. (PMID:11852067)
• The mast cell chymase A3255 allele was shown to have an effect on HDL cholesterol metabolism. (PMID:12047032)
• The local release of mast cell chymase has potentially profound effects on airway smooth muscle cell function by disruption of the cell-associated matrix and inhibition of epidermal growth factor-induced smooth muscle cell proliferation. (PMID:12097409)
• Results suggest the additive effect of angiotensin I-converting enzyme (ACE) and heart chymase (CMA) gene polymorphisms on the increase in left ventricular mass in NIDDM patients. (PMID:12165749)
• Chymase may play a role in heart remodeling by increasing Ang II formation and activating MMP-9, and the regulation of collagen I gene expression. (PMID:12359984)
• Both the ACE and chymase-like enzyme activities in the aneurysmal aortae were significantly higher than those in the control aortae. (PMID:12484503)
• Degradation of phospholipid transfer protein (PLTP) and PLTP-generated pre-beta-high density lipoprotein by this enzyme in mast cells impairs high affinity efflux of cholesterol from macrophage foam cells. (PMID:12531890)
• Interactions among the loops bordering and defining the active site appear to influence both the zymogen and the activated conformations of chymase in this model. (PMID:12614156)
• albumin is a substrate of human chymase (PMID:12815038)
• new class of chymase inhibitor through a substituent analysis of MWP00965 chemically synthesized (PMID:14592513)
• chymase depletes pre-beta-high density lipoprotein, which impairs ATP-binding cassette transporter A1- but not scavenger receptor class B type I-mediated lipid efflux to high density lipoprotein (PMID:14701812)
• MCT1 immunoreactivity was visible in blood vessel walls as early as the 13th week of gestation mainly in the visual cortical plate and subplate. (PMID:14757520)
• mast cell chymase-1 is unlikely to influence blood pressure levels in the Japanese population. (PMID:15106801)
• Bladder fibrosis may be mediated by mast cell chymase stimulation of collagen synthesis. (PMID:15227657)
• The synthesis of new potential inhibitors of human chymase is described (PMID:15449728)
• Tryptase and chymase and protein levels were determined in mast cells in fibrosarcoma. (PMID:15638376)
• mast cell chymase activates ERK and p38 probably through G-protein-coupled receptor, and the ERK but not p38 cascade may have a crucial role in chymase-induced migration of eosinophils (PMID:15919053)
• A novel (TG)n(GA)m repeat polymorphism 254 bp downstream of the mast cell chymase (CMA1) gene is associated with atopic asthma and total serum IgE levels. (PMID:15924217)
• Chymase-induced apoptosis of conjunctival epithelial cells represents anoikis, which is a slowly occurring apoptotic process induced by lack of adhesion to an extracellular matrix. (PMID:16020275)
• Significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema supports the hypothesis that CMA1 serves as candidate gene for atopic eczema. (PMID:16134991)
• activated human skin mast cells (MCs) convert CTAP-III into biologically active NAP-2 through proteolytic cleavage by released chymase. (PMID:16317101)
• The CMA1 polymorphisms studied do not contribute to disease susceptibility in Japanese or Dutch sarcoidosis patients. (PMID:16446531)
• AGEs, a hallmark of diabetes, induce chymase via the RAGE-ERK1/2 MAP kinase pathway. Chymase initiates an important alternative angiotensin II-generating pathway in diabetes and may play a critical role in diabetic vascular disease. (PMID:16520412)
• chymase in mast cells may have a role in inflammatory bowel disease (PMID:16786130)
• There was higher angiotensin-converting enzyme (ACE) and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. (PMID:16962475)
• cardiac chymase activity appears to be involved in cardiac remodelling–REVIEW (PMID:17199219)
• These observations suggest that mast cell chymase, possibly induced by interleukin-4-dependent phenotypic modulation, may be an important mediator in the inflammatory and fibrotic processes of idiopathic interstitial pneumonia in humans. (PMID:17334631)
• Chymase promoted the migration of vascular smooth muscle cells in the matrix-coated invasion chambers and activated promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth muscle cells. (PMID:17460374)
• chymase inactivates the FAK-mediated cell survival signaling (PMID:18079408)
• epithelial chymase is rapidly activated by a ligand-independent mechanism following mechanical stress via cytoskeletal and reactive oxygen species signaling and is associated with the onset of epithelial cell migration (PMID:18845543)
• In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. (PMID:18958543)
• positive association between the CMA1 -1903 G/A single nucleotide polymorphism and bronchial asthma in children in Egypt (PMID:18973102)
• Placenta-derived chymotrypsin-like protease contributes to the altered endothelial barrier function in preeclampsia. (PMID:19126871)
• After secretion by mast cells, alpha 2-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. (PMID:19380825)
• activation of endothelial CLP/chymase may directly relate to the increased inflammatory phenotypic changes in the vascular system in women with preeclampsia (PMID:19494363)
• The levels of tryptase and chymase expression are greatly increased in human lung tissue of anaphylactic shock. (PMID:19697770)
• Positions 143 (Arg) and 192 (Lys) in human mast cell chymase contribute to the strong preference for negatively charged amino acids at substrate position P2’. (PMID:20423454)
• Elevated maternal chymase activity and enhanced protease immunostaining in the maternal vessel endothelium may constitute the exacerbated inflammatory state and account for the increased vascular Ang II sensitivity in preeclampsia. (PMID:20670150)
• short tandem repeat genetic polymorphism is associated with bronchial asthma in a Swiss cohort study (PMID:20736038)
• Chymase rs1800875 polymorphism is associated with the progression of immunoglobulin A (IgA) nephropathy in Korean patients. (PMID:21150220)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cma1	ENSMUSG00000022225
rattus_norvegicus	Cma1	ENSRNOG00000020563

Paralogs (6): CTSG (ENSG00000100448), GZMH (ENSG00000100450), GZMB (ENSG00000100453), KLK6 (ENSG00000167755), KLK13 (ENSG00000167759), AZU1 (ENSG00000172232)

Protein

Protein identifiers

Chymase — P23946 (reviewed: P23946)

Alternative names: Alpha-chymase, Mast cell protease I

All UniProt accessions (1): P23946

UniProt curated annotations — full annotation on UniProt →

Function. Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.

Subcellular location. Secreted. Cytoplasmic granule.

Tissue specificity. Mast cells in lung, heart, skin and placenta. Expressed in both normal skin and in urticaria pigmentosa lesions.

Similarity. Belongs to the peptidase S1 family. Granzyme subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P23946-1	1	yes
P23946-2	2

RefSeq proteins (2): NP_001295012, NP_001827* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.39 — chymase (BRENDA: 13 organisms, 263 substrates, 307 inhibitors, 108 Km, 104 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
SUCCINYL-ALA-ALA-PRO-PHE-4-NITROANILIDE	0.663–0.991	6
ANGIOTENSIN I	0.0223–0.398	4
ALA-ALA-PRO-LEU-4-NITROANILIDE	1.02–1.55	3
ALA-ALA-PRO-MET-4-NITROANILIDE	0.97–27	3
ALA-ALA-PRO-PHE-4-NITROANILIDE	0.47–0.65	3
SUCCINYL-MET-VAL-PRO-PHE-4-NITROANILIDE	0.055–0.063	3
SUCCINYL-PHE-LEU-PHE-4-NITROANILIDE	0.023–0.091	3
SUCCINYL-PHE-PRO-PHE-4-NITROANILIDE	0.053–0.29	3
SUCCINYL-PHE-VAL-PRO-PHE-4-NITROANILIDE	0.056–0.17	3
SUCCINYL-THR-PRO-PHE-4-NITROANILIDE	0.25–0.28	3
SUCCINYL-VAL-PRO-LEU-4-NITROANILIDE	0.88–1.1	3
SUCCINYL-VAL-PRO-PHE-4-NITROANILIDE	0.093–0.12	3
METHOXYSUCCINYL-ARG-PRO-TYR-4-NITROANILIDE	0.3–1.8	2
SUCCINYL-ALA-PRO-PHE-4-NITROANILIDE	0.67–0.84	2
SUCCINYL-EPSILON-(2-PICOLINYL)LYS-VAL-PRO-PHE-4-	1–2.3	2

UniProt features (39 total): strand 15, disulfide bond 3, sequence variant 3, helix 3, turn 3, active site 3, sequence conflict 2, glycosylation site 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, domain 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7H66	X-RAY DIFFRACTION	1.13
7H68	X-RAY DIFFRACTION	1.25
7H6F	X-RAY DIFFRACTION	1.25
7H67	X-RAY DIFFRACTION	1.35
4AG1	X-RAY DIFFRACTION	1.4
4K60	X-RAY DIFFRACTION	1.5
4K69	X-RAY DIFFRACTION	1.5
4AFQ	X-RAY DIFFRACTION	1.51
7H62	X-RAY DIFFRACTION	1.61
7H6C	X-RAY DIFFRACTION	1.61
7H6D	X-RAY DIFFRACTION	1.64
7H63	X-RAY DIFFRACTION	1.65
7H69	X-RAY DIFFRACTION	1.67
7H64	X-RAY DIFFRACTION	1.68
7H6A	X-RAY DIFFRACTION	1.68
7H61	X-RAY DIFFRACTION	1.74
1NN6	X-RAY DIFFRACTION	1.75
9GCC	X-RAY DIFFRACTION	1.79
9GCD	X-RAY DIFFRACTION	1.8
3N7O	X-RAY DIFFRACTION	1.8
4AG2	X-RAY DIFFRACTION	1.8
4K5Z	X-RAY DIFFRACTION	1.8
5YJP	X-RAY DIFFRACTION	1.8
7H65	X-RAY DIFFRACTION	1.8
4AFU	X-RAY DIFFRACTION	1.82
7H60	X-RAY DIFFRACTION	1.88
1KLT	X-RAY DIFFRACTION	1.9
1T31	X-RAY DIFFRACTION	1.9
4AFS	X-RAY DIFFRACTION	1.9
5YJM	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23946-F1	91.55	0.84

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): 66 (charge relay system); 110 (charge relay system); 203 (charge relay system)

Disulfide bonds (3): 144–209, 175–188, 51–67

Glycosylation sites (2): 80, 103

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins

MSigDB gene sets: 169 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, MORF_ATRX, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr14q12

GO Biological Process (13): angiotensin maturation (GO:0002003), peptide metabolic process (GO:0006518), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), midbrain development (GO:0030901), basement membrane disassembly (GO:0034769), positive regulation of angiogenesis (GO:0045766), regulation of inflammatory response (GO:0050727), protein maturation (GO:0051604), cellular response to glucose stimulus (GO:0071333), cytokine precursor processing (GO:0140447), proteolysis (GO:0006508), protein processing (GO:0016485)

GO Molecular Function (6): endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptide binding (GO:0042277), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), secretory granule (GO:0030141), extracellular matrix (GO:0031012), cytoplasmic ribonucleoprotein granule (GO:0036464)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Degradation of the extracellular matrix	1
Peptide hormone metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	3
peptidase activity	2
cellular anatomical structure	2
cytoplasm	2
regulation of angiotensin levels in blood	1
peptide hormone processing	1
metabolic process	1
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
brain development	1
anatomical structure development	1
extracellular matrix disassembly	1
basement membrane organization	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
gene expression	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
cytokine production	1
signaling receptor ligand precursor processing	1
proteolysis	1
protein maturation	1
endopeptidase activity	1
serine-type peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
endomembrane system	1
secretory vesicle	1
external encapsulating structure	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

1634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMA1	CPA3	P15088	865
CMA1	ACE	P12821	843
CMA1	CPA4	Q9UI42	837
CMA1	AGT	P01019	792
CMA1	CTSC	P53634	752
CMA1	MS4A2	Q01362	740
CMA1	REN	P00797	726
CMA1	SERPINB4	P48594	691
CMA1	ATP6AP2	O75787	678
CMA1	COL6A5	A8TX70	650
CMA1	KITLG	P21583	645
CMA1	ATP7A	Q04656	642
CMA1	SRGN	P10124	639
CMA1	ACE2	Q9BYF1	612
CMA1	SERPINA1	P01009	603

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
MTMR11	HSPA8	psi-mi:“MI:0914”(association)	0.350
GALNT9	CMA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): RRS1 (Proximity Label-MS), ITIH2 (Affinity Capture-MS), CD109 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), CMA1 (Affinity Capture-MS), MANBA (Affinity Capture-MS), LOXL2 (Affinity Capture-MS)

ESM2 similar proteins: A7WPL7, O35164, O35205, O46683, O88780, P00770, P04187, P07288, P08883, P08884, P09582, P09650, P10144, P11032, P11034, P13366, P15119, P17977, P20151, P20718, P21812, P21842, P21844, P23946, P28293, P33619, P36368, P36369, P43430, P49862, P50339, P50340, P50341, P52195, P56435, P79204, P80219, P80931, P85202, P97592

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00752, P00760, P00761, P00762, P00763, P00764, P00770, P00772, P00773, P04187, P06870, P06871, P07146, P07288, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12323, P12544, P12788, P13366, P15119, P16049, P17977, P18291

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CMA1	“up-regulates activity”	EDN3	cleavage
CMA1	“up-regulates activity”	EDN1	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

473 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24508174:TCA:T	donor_loss	1.0000
14:24508175:CAC:C	donor_loss	1.0000
14:24505658:CC:C	acceptor_gain	0.9900
14:24505658:CCCTG:C	acceptor_loss	0.9900
14:24505659:CC:C	acceptor_gain	0.9900
14:24505659:CCTGT:C	acceptor_loss	0.9900
14:24508176:A:AC	donor_gain	0.9900
14:24508176:AC:A	donor_gain	0.9900
14:24508177:C:CA	donor_gain	0.9900
14:24508177:CC:C	donor_gain	0.9900
14:24508177:CCA:C	donor_gain	0.9900
14:24508177:CCAG:C	donor_gain	0.9900
14:24505655:TCTCC:T	acceptor_gain	0.9800
14:24505656:CTCC:C	acceptor_gain	0.9800
14:24505656:CTCCC:C	acceptor_gain	0.9800
14:24505657:TCC:T	acceptor_gain	0.9800
14:24505657:TCCCT:T	acceptor_gain	0.9800
14:24505658:CCC:C	acceptor_gain	0.9800
14:24505660:C:CC	acceptor_gain	0.9800
14:24505662:G:C	acceptor_gain	0.9800
14:24505662:G:GC	acceptor_gain	0.9800
14:24506600:TAGAC:T	acceptor_gain	0.9800
14:24506603:ACC:A	acceptor_loss	0.9800
14:24506604:CC:C	acceptor_loss	0.9800
14:24506605:C:A	acceptor_loss	0.9800
14:24506605:C:CC	acceptor_gain	0.9800
14:24506606:T:C	acceptor_loss	0.9800
14:24507358:T:TA	donor_gain	0.9800
14:24508170:ATACT:A	donor_loss	0.9800
14:24508172:ACT:A	donor_loss	0.9800

AlphaMissense

1596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24506181:C:A	W149C	0.993
14:24506181:C:G	W149C	0.993
14:24505570:G:C	F230L	0.990
14:24505570:G:T	F230L	0.990
14:24505572:A:G	F230L	0.990
14:24506485:T:A	D110V	0.990
14:24506485:T:G	D110A	0.989
14:24505543:C:A	W239C	0.985
14:24505543:C:G	W239C	0.985
14:24506065:C:G	C188S	0.985
14:24506066:A:T	C188S	0.985
14:24506593:A:T	V74D	0.982
14:24506183:A:G	W149R	0.980
14:24506183:A:T	W149R	0.980
14:24506476:A:G	L113S	0.980
14:24506484:A:C	D110E	0.979
14:24506484:A:T	D110E	0.979
14:24506486:C:G	D110H	0.978
14:24505655:T:A	D202V	0.976
14:24506281:A:G	L116S	0.976
14:24507365:C:G	C67S	0.976
14:24507366:A:T	C67S	0.976
14:24505654:G:C	D202E	0.975
14:24505654:G:T	D202E	0.975
14:24506485:T:C	D110G	0.975
14:24505655:T:G	D202A	0.974
14:24506104:C:G	C175S	0.974
14:24506105:A:T	C175S	0.974
14:24506473:A:G	L114P	0.974
14:24507403:G:C	F54L	0.974

dbSNP variants (sampled 300 via entrez): RS1000638219 (14:24507697 C>G,T), RS1000704967 (14:24509008 T>C), RS1001010276 (14:24507949 C>A), RS1001312919 (14:24510243 A>G,T), RS1001361320 (14:24504864 C>T), RS1001413707 (14:24505147 T>A), RS1001591456 (14:24507217 C>T), RS1001813145 (14:24507430 G>A,C,T), RS1003737298 (14:24508486 CT>C), RS1003933786 (14:24509053 A>G,T), RS1006206048 (14:24510146 G>C), RS1006272192 (14:24505068 A>G), RS1006992161 (14:24507079 C>G,T), RS1007325607 (14:24505895 A>C,G), RS1007543810 (14:24505777 C>A,G,T)

Disease associations

OMIM: gene MIM:118938 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4068 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 21,146 (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
CHEMBL218394	BOCEPREVIR	4	2,760
CHEMBL231813	TELAPREVIR	4	3,301
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL270515	DELANZOMIB	2	1,883
CHEMBL4297596	FULACIMSTAT	2	82

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

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

Ligand	Action	Affinity	Parameter
NK3201	Inhibition	8.6	pIC50
JNJ-10311795	Inhibition	8.3	pIC50
TY-51469	Inhibition	8.15	pIC50
compound 7f [PMID: 29191554]	Inhibition	8.05	pIC50

Binding affinities (BindingDB)

226 measured of 248 human assays (248 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[2,4-dioxo-1-[(1,4,6-trimethylindol-3-yl)methyl]pyrido[3,2-d]pyrimidin-3-yl]heptanoic acid	IC50	0.3 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[2,4-dioxo-1-[(1,4,6-trimethylindol-3-yl)methyl]pyrido[3,2-d]pyrimidin-3-yl]pentanoic acid	IC50	0.4 nM	US-8501749: Azaquinazolinediones chymase inhibitors
3-cyclopropyl-3-[2,4-dioxo-1-[(1,4,6-trimethylindol-3-yl)methyl]pyrido[3,2-d]pyrimidin-3-yl]propanoic acid	IC50	0.7 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[2,4-dioxo-1-[(1,4,6-trimethylindol-3-yl)methyl]pyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	0.7 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2R)-2-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]hexanoic acid	IC50	0.9 nM	US-8501749: Azaquinazolinediones chymase inhibitors
3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]hexanoic acid	IC50	1.3 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]pentanoic acid	IC50	1.4 nM	US-8501749: Azaquinazolinediones chymase inhibitors
3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]heptanoic acid	IC50	1.4 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2S)-2-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	2.1 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]pentanoic acid	IC50	2.2 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	2.5 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2R)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]hexanoic acid	IC50	2.6 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2R)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]butanoic acid	IC50	2.6 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2S)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]butanoic acid	IC50	2.7 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3S)-3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]pentanoic acid	IC50	3 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-[4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-3-[(3,5-difluorophenoxy)amino]-7-oxo-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]ethyl]phenyl]acetic acid	IC50	3 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
(2S)-2-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]-2-phenylacetic acid	IC50	3.1 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2R)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	4 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-amino-4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-3-[(3,5-difluorophenoxy)amino]-7-oxo-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]ethyl]benzoic acid	IC50	4 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
(2S)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	4.8 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]acetic acid	IC50	6.1 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl]pentanoic acid	IC50	6.1 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2S)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]butanoic acid	IC50	7 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(2S)-2-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]hexanoic acid	IC50	7 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-amino-4-[(1R)-1-[[7-[(5-chloro-2-methoxyphenyl)methyl]-4,8-dioxo-7,10-dihydro-6H-[1,2,4]oxadiazino[4,3-a][1,4]diazepine-9-carbonyl]amino]butyl]benzoic acid	IC50	7 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
2-[4-[(1,4-dimethylindol-3-yl)methyl]-1-oxophthalazin-2-yl]-2-phenylacetic acid	IC50	7 nM	US-8969348: Chymase inhibitors
(3S)-3-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl]pentanoic acid	IC50	7.4 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3S)-3-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl]pentanoic acid	IC50	8 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-amino-4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-7-oxo-3-(phenoxyamino)-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]propyl]benzoic acid	IC50	9 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
2-[4-[(1,4-dimethylindol-3-yl)methyl]-1-oxophthalazin-2-yl]pentanoic acid	IC50	9 nM	US-8969348: Chymase inhibitors
2-[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]acetic acid	IC50	9.6 nM	US-8501749: Azaquinazolinediones chymase inhibitors
(3R)-3-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	9.9 nM	US-8501749: Azaquinazolinediones chymase inhibitors
2-amino-4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-3-[(4-fluorophenoxy)amino]-7-oxo-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]ethyl]benzoic acid	IC50	10 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
2-amino-4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-7-oxo-3-(pyridin-2-yloxyamino)-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]ethyl]benzoic acid	IC50	10 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
2-[4-[(1R)-1-[[6-[(5-chloro-2-methoxyphenyl)methyl]-3-[(4-fluorophenoxy)amino]-7-oxo-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]ethyl]phenyl]acetic acid	IC50	10 nM	US-8846660: Seven-membered ring compound and pharmaceutical use therefor
2,4-Dioxo-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-3-[5-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (racemate)	IC50	10 nM	US-9751843: Substituted uracils and use thereof
2-[[1-[(1,4-dimethylindol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]methyl]hexanoic acid	IC50	11 nM	US-8501749: Azaquinazolinediones chymase inhibitors
1-[3,5-Dichloro-4-(2-oxoimidazolidin-1-yl)phenyl]-3-[2-methyl-3-(trifluoromethyl)benzyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	11 nM	US-9751843: Substituted uracils and use thereof
1-[3-Chloro-4-(2-oxoimidazolidin-1-yl)phenyl]-3-[2-methyl-3-(trifluoromethyl)benzyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	12 nM	US-9751843: Substituted uracils and use thereof
1-[3-Chloro-4-(2-oxoimidazolidin-1-yl)phenyl]-3-[2-chloro-3-(trifluoromethyl)benzyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	13 nM	US-9751843: Substituted uracils and use thereof
1-[2-Fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer)	IC50	13 nM	US-9751843: Substituted uracils and use thereof
1-[3-Chloro-4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-3-[2-methyl-3-(trifluoromethyl)benzyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	16 nM	US-9751843: Substituted uracils and use thereof
3-[2-Chloro-3-(trifluoromethyl)benzyl]-1-[3,5-dichloro-4-(2-oxoimidazolidin-1-yl)phenyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	16 nM	US-9751843: Substituted uracils and use thereof
(3S)-3-[1-[(4,6-dimethyl-1,2-benzothiazol-3-yl)methyl]-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl]pentanoic acid	IC50	17 nM	US-8501749: Azaquinazolinediones chymase inhibitors
1-[3-Chloro-4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-3-[2-chloro-3-(trifluoromethyl)benzyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	17 nM	US-9751843: Substituted uracils and use thereof
2,4-Dioxo-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer)	IC50	17 nM	US-9751843: Substituted uracils and use thereof
3-[2-Chloro-3-(trifluoromethyl)benzyl]-2,4-dioxo-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid	IC50	18 nM	US-9751843: Substituted uracils and use thereof
1-(3,4-Dimethoxyphenyl)-2,4-dioxo-3-[4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (racemate)	IC50	18 nM	US-9751843: Substituted uracils and use thereof
6-[(4-chloro-5-fluoro-2-methoxyphenyl)methyl]-4-(4-chlorophenyl)sulfonyl-1,4-diazepane-2,5-dione	IC50	19 nM	US-8507714: 7-membered ring compound and method of production and pharmaceutical application thereof
methyl 2-[(2R,6S)-1-(4-chlorophenyl)sulfonyl-6-[(5-fluoro-2-methoxyphenyl)methyl]-3,7-dioxo-1,4-diazepan-2-yl]acetate	IC50	19 nM	US-8507714: 7-membered ring compound and method of production and pharmaceutical application thereof

ChEMBL bioactivities

736 potent at pChembl≥5 of 775 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	Ki	0.22	nM	CHEMBL4592765
9.52	IC50	0.3	nM	CHEMBL3640120
9.40	IC50	0.4	nM	BI-1942
9.34	IC50	0.46	nM	CHEMBL1631751
9.15	IC50	0.7	nM	CHEMBL3640115
9.15	IC50	0.7	nM	CHEMBL3640118
9.07	IC50	0.85	nM	CHEMBL44950
9.05	IC50	0.9	nM	CHEMBL3640105
8.95	Ki	1.12	nM	CHEMBL26285
8.89	Ki	1.3	nM	CHEMBL353816
8.89	IC50	1.3	nM	CHEMBL3640121
8.85	IC50	1.4	nM	CHEMBL3640110
8.85	IC50	1.4	nM	CHEMBL3640119
8.77	Ki	1.7	nM	CHEMBL4450993
8.74	Ki	1.8	nM	CHEMBL4560112
8.70	IC50	2	nM	CHEMBL48083
8.68	IC50	2.1	nM	CHEMBL3640102
8.66	IC50	2.2	nM	CHEMBL3640111
8.66	Ki	2.2	nM	CHEMBL4465306
8.64	Ki	2.3	nM	CHEMBL374027
8.64	Ki	2.3	nM	CHEMBL424224
8.64	IC50	2.3	nM	CHEMBL45780
8.60	IC50	2.5	nM	CHEMBL3639389
8.59	IC50	2.6	nM	CHEMBL3640100
8.59	IC50	2.6	nM	CHEMBL3640114
8.58	Ki	2.62	nM	CHEMBL24734
8.57	IC50	2.7	nM	CHEMBL3640117
8.52	Ki	3	nM	CHEMBL355430
8.52	IC50	3	nM	CHEMBL3640107
8.52	IC50	3	nM	CHEMBL3657195
8.51	Ki	3.1	nM	CHEMBL170200
8.51	IC50	3.1	nM	CHEMBL3640095
8.51	IC50	3.1	nM	CHEMBL1631756
8.46	IC50	3.5	nM	CHEMBL373916
8.45	Ki	3.56	nM	CHEMBL26448
8.43	Ki	3.68	nM	CHEMBL281124
8.41	Ki	3.9	nM	CHEMBL436061
8.40	IC50	4	nM	CHEMBL3640103
8.40	IC50	4	nM	CHEMBL3653523
8.40	IC50	4	nM	CHEMBL47394
8.40	IC50	4	nM	FULACIMSTAT
8.35	IC50	4.5	nM	CHEMBL374027
8.32	IC50	4.8	nM	CHEMBL3640104
8.32	Ki	4.8	nM	CHEMBL402185
8.31	Ki	4.85	nM	CHEMBL26285
8.30	IC50	5	nM	CHEMBL335675
8.25	IC50	5.6	nM	CHEMBL436591
8.25	Ki	5.6	nM	CHEMBL287318
8.25	Ki	5.6	nM	CHEMBL169707
8.25	Ki	5.6	nM	CHEMBL256270

PubChem BioAssay actives

417 with measured affinity, of 646 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-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0002	uM
(2R,3S)-3-benzyl-2-[4-(4-methylpiperazin-1-yl)phenoxy]-4-oxo-N-[(1R)-1-phenylethyl]azetidine-1-carboxamide	547676: Inhibition of human Chymase	ic50	0.0005	uM
1,3-bis(1,3-benzodioxol-5-ylmethyl)-1,3-diazetidine-2,4-dione	200375: Compound was evaluated for its inhibitory activity against human Serine protease chymase	ic50	0.0008	uM
methyl 2-[2-[[2-[5-amino-2-(3-methoxyphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	219699: Inhibitory activity against canine skin chymase	ki	0.0011	uM
3-[[2,2-difluoro-4-[[(2S)-1-[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]pyrrolidine-2-carbonyl]amino]-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0013	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-34,49-dibenzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-28-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0017	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-34-(3-carbamimidamidopropyl)-19-(2-carboxyethyl)-40-(carboxymethyl)-25-[(4-chlorophenyl)methyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0018	uM
1,3-bis[(4-methoxyphenyl)methyl]-1,3-diazetidine-2,4-dione	200375: Compound was evaluated for its inhibitory activity against human Serine protease chymase	ic50	0.0020	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-34-(3-carbamimidamidopropyl)-19-(2-carboxyethyl)-40-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-methylphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0022	uM
[2-[3-[methyl-[1-(naphthalene-2-carbonyl)piperidin-4-yl]carbamoyl]naphthalen-2-yl]-1-naphthalen-1-yl-2-oxoethyl]phosphonic acid	281265: Inhibition of human skin chymase	ki	0.0023	uM
1,3-bis[(3-methoxyphenyl)methyl]-1,3-diazetidine-2,4-dione	200375: Compound was evaluated for its inhibitory activity against human Serine protease chymase	ic50	0.0023	uM
(1-naphthalen-1-yl-2-naphthalen-2-yl-2-oxoethyl)phosphonic acid	1530545: Inhibition of chymase in human mast cells using Suc-Ala-Ala-Pro-Phe-(p-nitroanilide) as substrate for 15 mins by spectrophotometric method	ki	0.0023	uM
4-[[2-[5-amino-2-(3-chlorophenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0026	uM
(4S)-5-[(2S)-2-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-[[(2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoic acid	52298: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0030	uM
3-[[4-[[(2S)-1-[(2S)-2-benzamido-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0031	uM
4-[(2R,3S)-1-(benzhydrylcarbamoyl)-3-[(2-ethoxyphenyl)methyl]-4-oxoazetidin-2-yl]oxybenzoic acid	547676: Inhibition of human Chymase	ic50	0.0031	uM
[1-(5-chloro-1-benzothiophen-3-yl)-2-[[(E)-2-(3-chlorophenyl)ethenyl]amino]-2-oxoethyl]-methylphosphinic acid	281265: Inhibition of human skin chymase	ic50	0.0035	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-[2-(azepan-1-yl)-2-oxoethyl]-2,2-difluoro-3-oxo-5-phenylpentanamide	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0036	uM
methyl 2-[2-[[2-[5-amino-2-(4-fluorophenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	219699: Inhibitory activity against canine skin chymase	ki	0.0037	uM
3-[[4-[[(2S)-1-[4-carboxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52298: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0039	uM
1,3-dibenzyl-1,3-diazetidine-2,4-dione	200375: Compound was evaluated for its inhibitory activity against human Serine protease chymase	ic50	0.0040	uM
methyl 2-[(2S)-2-[[2-[5-amino-2-(3-methoxyphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	321215: Inhibition of human chymase	ki	0.0048	uM
(3-benzamido-2,2-dimethylheptanoyl) 3-benzamido-2,2-dimethylheptanoate	223378: Inhibitory activity against human chymase (h-chymase)	ic50	0.0050	uM
3-[[2,2-difluoro-4-[[(2S)-1-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-3-oxo-5-phenylpentanoyl]amino]benzoic acid	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0056	uM
methyl 2-[2-[[2-(5-amino-6-oxo-2-phenylpyrimidin-1-yl)acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	200388: Inhibitory activity evaluated against chymase from human heart.	ki	0.0056	uM
methyl 2-[2-[[2-[5-amino-2-(3-aminophenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	200388: Inhibitory activity evaluated against chymase from human heart.	ki	0.0056	uM
[3-(butanoylamino)-2,2-dimethyl-5-phenylpentanoyl] 3-(butanoylamino)-2,2-dimethyl-5-phenylpentanoate	223378: Inhibitory activity against human chymase (h-chymase)	ic50	0.0056	uM
3-[[2,2-difluoro-4-[[(2S)-1-[3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52298: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0056	uM
methyl 2-[(2S)-2-[[2-(5-amino-6-oxo-2-phenylpyrimidin-1-yl)acetyl]amino]-3-phenylpropanoyl]-1,3-benzoxazole-5-carboxylate	321215: Inhibition of human chymase	ki	0.0056	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0057	uM
2-[5-[[(6R,7R)-7-methoxy-7-[(2-methoxybenzoyl)amino]-2-[(3-methylphenyl)methoxycarbonyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-en-3-yl]methylsulfanyl]tetrazol-1-yl]acetic acid	200382: Inhibition of human Serine protease chymase	ic50	0.0060	uM
2-[3-[[(6R,7R)-7-methoxy-7-[(2-methoxybenzoyl)amino]-2-[(3-methylphenyl)methoxycarbonyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-en-3-yl]methylsulfanyl]-1,2,4-triazol-4-yl]acetic acid	200383: Inhibitory activity against human serine protease chymase	ic50	0.0060	uM
5-[[4-[[(2S)-1-[4-carboxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]thiophene-3-carboxylic acid	52298: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0060	uM
3-[[4-[[(2S)-1-[(2S)-2-(benzenesulfonamido)-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0063	uM
methyl 2-[[2,2-difluoro-4-[[(2S)-1-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-3-oxo-5-phenylpentanoyl]amino]acetate	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0065	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-34-(3-carbamimidamidopropyl)-19-(2-carboxyethyl)-40-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0066	uM
5-[(2S)-2-[[5-[3-(carboxymethyl)anilino]-4,4-difluoro-3,5-dioxo-1-phenylpentan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid	52298: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0067	uM
4-[[2,2-difluoro-4-[[(2S)-1-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carbonyl]amino]-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0068	uM
3-[[4-[[(2S)-1-[(2S)-2-acetamido-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0071	uM
tert-butyl N-[(2S)-1-[(2S)-2-[[5-(benzylamino)-4,4-difluoro-3,5-dioxo-1-phenylpentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate	52297: Compound was evaluated for inhibitory activity against human heart chymase (HHC)	ki	0.0074	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-19-(2-carboxyethyl)-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0075	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-[2-(ethylamino)-2-oxoethyl]-2,2-difluoro-3-oxo-5-phenylpentanamide	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0077	uM
2-amino-4-[(1R)-1-[[(6R)-6-[(5-chloro-2-methoxyphenyl)methyl]-7-oxo-3-(phenoxyamino)-5,6-dihydro-2H-1,4-diazepine-1-carbonyl]amino]propyl]benzoic acid	1368432: Inhibition of recombinant human chymase pre-incubated for 10 mins before Suc-Ala-Ala-Pro-Phe-MCA substrate addition and measured after 10 mins by fluorescence assay	ic50	0.0089	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-[2-(diethylamino)-2-oxoethyl]-2,2-difluoro-3-oxo-5-phenylpentanamide	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0093	uM
(2S)-2-[[(1S)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid	1350777: Inhibition of chymase (unknown origin) by fluorescence assay	ic50	0.0094	uM
3-[[4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0097	uM
[1-(5-chloro-1-methylindol-3-yl)-2-(naphthalen-2-ylamino)-2-oxoethyl]-methylphosphinic acid	281265: Inhibition of human skin chymase	ic50	0.0100	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-34,49-dibenzyl-4-[(2S)-butan-2-yl]-19-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-28-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1582054: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells using NleTDY-pNA as substrate assessed as cleavage of pNA at pH 7.2 and 298 K by spectrophotometry analysis	ki	0.0100	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-3-oxo-N-(2-oxo-2-piperidin-1-ylethyl)-5-phenylpentanamide	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0102	uM
methyl 2-[[4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]acetate	200387: In vitro inhibitory activity was determined against human heart chymase	ki	0.0102	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
butyraldehyde	increases expression	1
CGP 52608	increases reaction, affects binding	1
(2-(5-amino-2-(4-fluorophenyl)-1,6-dihydro-6-oxo-1-pyrimidinyl)-N-(1-((5-methoxycarbonyl-2-benzoxazolyl)carbonyl)-2-phenylethyl)acetamide)	decreases activity	1
Malathion	decreases expression	1
Paraquat	increases expression, increases reaction	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

93 unique, capped per target: 89 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039252	Binding	Inhibition of chymase after 10 to 15 mins by fluorescence assay	Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. — J Med Chem
CHEMBL4380410	ADMET	Substrate activity at recombinant human chymase expressed in Pichia pastoris X-33 cells assessed as Km by spectrophotometry analysis	Binding Loop Substitutions in the Cyclic Peptide SFTI-1 Generate Potent and Selective Chymase Inhibitors. — J Med Chem

Clinical trials (associated diseases)

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