CTRC

Summary

CTRC (chymotrypsin C, HGNC:2523) is a protein-coding gene on chromosome 1p36.21, encoding Chymotrypsin-C (Q99895). Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors.

This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined.

Source: NCBI Gene 11330 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary chronic pancreatitis (Definitive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 757 total — 8 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2523
Approved symbol	CTRC
Name	chymotrypsin C
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Aliases	CLCR, ELA4
Ensembl gene	ENSG00000162438
Ensembl biotype	protein_coding
OMIM	601405
Entrez	11330

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000375943, ENST00000375949, ENST00000476813, ENST00000483406

RefSeq mRNA: 1 — MANE Select: NM_007272 NM_007272

CCDS: CCDS156

Canonical transcript exons

ENST00000375949 — 8 exons

Exon	Start	End
ENSE00001065204	15440300	15440391
ENSE00001544738	15438443	15438504
ENSE00001631925	15444606	15444751
ENSE00003501216	15440493	15440590
ENSE00003507823	15446575	15449242
ENSE00003524570	15445597	15445749
ENSE00003545227	15443419	15443555
ENSE00003653020	15442447	15442572

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 37.7062 / max 37977.3610, expressed in 21 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
857	37.4435	20
201370	0.1652	3
858	0.0350	3
201371	0.0339	4
201369	0.0286	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.92	gold quality
pancreas	UBERON:0001264	98.70	gold quality
islet of Langerhans	UBERON:0000006	97.44	gold quality
epithelial cell of pancreas	CL:0000083	89.80	gold quality
type B pancreatic cell	CL:0000169	88.94	gold quality
pancreatic ductal cell	CL:0002079	81.87	silver quality
olfactory bulb	UBERON:0002264	78.82	gold quality
diaphragm	UBERON:0001103	75.14	gold quality
endometrium epithelium	UBERON:0004811	72.59	gold quality
right coronary artery	UBERON:0001625	72.02	gold quality
ectocervix	UBERON:0012249	71.73	gold quality
descending thoracic aorta	UBERON:0002345	71.69	gold quality
granulocyte	CL:0000094	70.95	gold quality
right lobe of liver	UBERON:0001114	70.64	gold quality
triceps brachii	UBERON:0001509	70.11	gold quality
gluteal muscle	UBERON:0002000	69.83	gold quality
myocardium	UBERON:0002349	69.38	gold quality
left ventricle myocardium	UBERON:0006566	68.81	gold quality
fundus of stomach	UBERON:0001160	68.77	gold quality
endocervix	UBERON:0000458	68.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	68.58	gold quality
left uterine tube	UBERON:0001303	68.05	gold quality
tibialis anterior	UBERON:0001385	67.70	silver quality
spleen	UBERON:0002106	67.67	gold quality
metanephros cortex	UBERON:0010533	67.62	gold quality
right adrenal gland	UBERON:0001233	67.45	gold quality
lower esophagus mucosa	UBERON:0035834	67.43	gold quality
body of stomach	UBERON:0001161	67.41	gold quality
duodenum	UBERON:0002114	67.32	gold quality
right uterine tube	UBERON:0001302	67.18	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	27102.11
E-MTAB-5061	yes	5567.81
E-ENAD-27	yes	7.76
E-HCAD-31	yes	4.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 37)

• A key regulator of activation and degradation of cationic trypsin; facilitates trypsinogen activation in the duodenum, and promotes trypsin degradation in the lower intestines as a function of decreasing luminal calcium ion concentrations. (PMID:17592142)
• Study analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C in German subjects with idiopathic or hereditary chronic pancreatitis; 2 alterations in this gene were significantly overrepresented in the pancreatitis group. (PMID:18059268)
• The contribution of CTRC variants to tropical calcific pancreatitis (TCP) is relatively small, but the identification of novel loss-of-function variants (p.G61R) underscores the importance of the trypsinogen pathway in causing TCP. (PMID:19404200)
• Novel CTRC gene variations and single nucleotide polymorphisms are associated with chymotrypsin C in a Chinese population. (PMID:19407484)
• CTRC (p.R254W) mutation might contribute to the panel of mutations that have been reported to elevate pancreatitis susceptibility in primary hyperparathyroidism. (PMID:20625975)
• Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2. (PMID:21098023)
• review of its association with chronic pancreatitis in the Asia Pacific region (PMID:21323990)
• speculated that chymotrypsin C might regulate pancreatic cancer cell migration in relation to cytokeratin 18 expression (PMID:21460362)
• Review: summarize the functional defects associated with CTRC mutations in chronic pancreatitis. (PMID:21631589)
• Frequencies of CFTR variants p.R75Q, p.I148T, 5T-allele and p.E528E were comparable in patients and controls. We identified 103 CFTR variants, which represents a 2.7-fold risk increase (p<0.0001). (PMID:22427236)
• hereditary pancreatitis is caused by CTRC-dependent dysregulation of cationic trypsinogen autoactivation, which results in elevated trypsin levels in the pancreas. (PMID:22539344)
• This study on a large cohort of tropical calcific pancreatitis patients provides evidence of allelic heterogeneity and confirms that CTRC variants play a significant role in its pathogenesis. (PMID:22580415)
• Chymotrypsin C variants reveals distinct loss-of-function mechanisms associated with chronic pancreatitis risk. (PMID:22942235)
• In Japanese, 5 novel missense variants in heterozygous form were found in CTRC. (PMID:23135764)
• long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels (PMID:23430245)
• Rare CTRC genotypes contributed to the development of idiopathic chronic pancreatitis in 4.3% of cases. (PMID:23951356)
• None of the selected 121 pancreatic cancer samples showed a pancreatitis-predisposing mutation in the CTRC gene. (PMID:25003218)
• In Israel, pediatric as well as adult recurrent acute pancreatitis and chronic pancreatitis are often associated with cationic trypsinogen, serine protease inhibitor Kazal type 1, CTRC, or Cystic Fibrosis Transmembrane Conductance Regulator mutations. (PMID:25383785)
• Loss-of-function mutations in CTRC increase the risk for chronic pancreatitis. Describe functional analysis of eight previously uncharacterized natural CTRC variants tested for potential defects in secretion, proteolytic stability, and catalytic activity. (PMID:26013824)
• Expression of endoplasmic reticulum stress associated CTRC mutants reduces the levels of acetylated tubulin by increasing both the levels and phosphorylation of the deacetylase SIRT2. (PMID:26022124)
• Mutations in SPINK 1, CFTR and CTRC were detected in 6.3%, 2.3% and 1.8% of patients with acute pancreatitis versus 3.2%, 3.8% and 1.2% of controls. No relationship was found between the detected mutations and severity of pancreatitis. (PMID:26100556)
• Letter: CTRC intron mutations associated with acute or chronic pancreatitis. (PMID:26166474)
• Human anionic trypsinogen is controlled by CTRC in a manner that individual natural mutations are unlikely to increase stability enough to promote intra-pancreatic activation. (PMID:27129265)
• Gene mutations were present in PRSS1 in 26 patients with acute recurrent and chronic pancreatitis, SPINK1 in 23, CTRC in 3, and CPA1 in 5. In the 31 patients with mutations in SPINK1, CTRC, or CPA1, 16 (51.6%) had homozygous or heterozygous mutations with other mutations. (PMID:27409067)
• One patient carried a heterozygous CTRC p.P249L pathogenic variant, which is a known high-risk variant for pancreatitis. (PMID:27578509)
• CTRC polymorphism increases the risk of an acute pancreatitis occurrence and together with the SPINK 1 mutation, may be responsible for a more severe course of the disease. (PMID:28095786)
• Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. (PMID:28502372)
• CTRC variants, including p.Gly60Gly (c.180C>T) variant are significant chronic pancreatitis risk factors in pediatric patients. Screening for CTRC variants should be always considered in routine molecular diagnostics in early onset chronic pancreatitis. (PMID:28968289)
• Our preliminary results show that the CTRC polymorphism p.G60= (c.180C>T) is frequent in patients with pancreatic cancer. However, further research is needed to verify our findings. (PMID:29154238)
• No relationship between the c.738_761del and p.Arg254Trp mutations and the development of alcoholic chronic pancreatitis was found (PMID:30277669)
• Chronic pancreatitis with polycystic kidney disease: A rare coincidence? (PMID:31862184)
• Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation. (PMID:32014997)
• Association between genetic variants in CYP2E1 and CTRC genes and susceptibility to alcoholic pancreatitis: A systematic review and meta-analysis. (PMID:32045777)
• Clinical interpretation of SPINK1 and CTRC variants in pancreatitis. (PMID:32948427)
• Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis. (PMID:35594281)
• Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis. (PMID:37321941)
• Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases. (PMID:38876922)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Ctrc	ENSRNOG00000013745
drosophila_melanogaster	CG11912	FBGN0031248

Paralogs (2): CTRB1 (ENSG00000168925), CTRB2 (ENSG00000168928)

Protein

Protein identifiers

Chymotrypsin-C — Q99895 (reviewed: Q99895)

Alternative names: Caldecrin

All UniProt accessions (2): Q99895, Q68DR9

UniProt curated annotations — full annotation on UniProt →

Function. Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalcemic activity.

Tissue specificity. Pancreas.

Disease relevance. Pancreatitis, hereditary (PCTT) [MIM:167800] A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. Disease susceptibility is associated with variants affecting the gene represented in this entry. Loss-of-function CTRC variants predispose to pancreatitis by diminishing its protective trypsin-degrading activity. They cause loss of function by one or more of three mechanisms: reduced secretion, catalytic defect and increased degradation by trypsin.

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

RefSeq proteins (1): NP_009203* (*=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
IPR050850	Peptidase_S1_Elastase_sf	Family

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.2 — chymotrypsin C (BRENDA: 5 organisms, 49 substrates, 4 inhibitors, 48 Km, 47 kcat entries)

Substrate kinetics (BRENDA)

24 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	0.013–1.539	15
SUCCINYL-ALA-ALA-PRO-PHE-4-NITROANILIDE	0.0153–0.0472	10
BENZOYL-L-MET ETHYL ESTER	10–17	2
N-SUCCINYL-ALA-ALA-PRO-PHE-4-NITROANILIDE	0.0105–0.0134	2
ACETYL-L-LEU METHYL ESTER	10	1
ACETYL-L-TRP ETHYL ESTER	2.1	1
ACETYL-TYR ETHYL ESTER	13	1
BENZOYL-L-LEU ETHYL ESTER	28	1
BENZOYL-L-LEU METHYL ESTER	0.4	1
BENZOYL-L-PHE ETHYL ESTER	0.85	1
BENZOYL-L-TYR ETHYL ESTER	2	1
BENZYLOXYCARBONYL-L-LEU-GLY-AMIDE	15	1
N-ACETYL-TYR ETHYL ESTER	20	1
N-SUCCINYL-L-ALA-ALA-PRO-LEU-P-NITROANILIDE	0.0002	1
SUCCINYL-ALA-ALA-PRO-ALA 4-NITROANILIDE	0.392	1

UniProt features (78 total): sequence variant 38, strand 16, disulfide bond 5, helix 5, active site 3, glycosylation site 3, sequence conflict 2, turn 2, signal peptide 1, propeptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4H4F	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99895-F1	94.03	0.92

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): 74 (charge relay system); 121 (charge relay system); 216 (charge relay system)

Disulfide bonds (5): 17–141, 59–75, 155–222, 186–202, 212–243

Glycosylation sites (3): 25, 52, 226

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 129 (showing top): LEE_LIVER_CANCER_CIPROFIBRATE_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_109, LEE_LIVER_CANCER_DENA_DN, GOBP_MONOATOMIC_ION_HOMEOSTASIS, LEE_LIVER_CANCER_E2F1_DN, GOBP_HOMEOSTATIC_PROCESS, PID_UPA_UPAR_PATHWAY, GOBP_CHEMICAL_HOMEOSTASIS, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, LEE_LIVER_CANCER_MYC_DN, YOSHIMURA_MAPK8_TARGETS_UP, chr1p36, SU_PANCREAS

GO Biological Process (2): proteolysis (GO:0006508), intracellular calcium ion homeostasis (GO:0006874)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (0):

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
binding	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1

Protein interactions and networks

STRING

649 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTRC	SPINK1	P00995	931
CTRC	CPA1	P15085	810
CTRC	CFTR	P13569	775
CTRC	HTRA1	Q92743	649
CTRC	STATH	P02808	588
CTRC	CPA2	P48052	523
CTRC	CEL	P19835	493
CTRC	CASR	P41180	486
CTRC	CLDN2	P57739	474
CTRC	HEXD	Q8WVB3	474
CTRC	PLG	P00747	439
CTRC	PSMB2	P31145	433
CTRC	CTSB	P07858	415
CTRC	CPB1	P15086	394
CTRC	PNLIP	P16233	372

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CTRC	SUMF1	psi-mi:“MI:0915”(physical association)	0.590
	CTRC	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	CTRC	psi-mi:“MI:0915”(physical association)	0.560
CTRC		psi-mi:“MI:0915”(physical association)	0.560
CTRC	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	CTRC	psi-mi:“MI:0915”(physical association)	0.560
MDFI	CTRC	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	CTRC	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CTRC	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	CTRC	psi-mi:“MI:0915”(physical association)	0.560
KRT34	CTRC	psi-mi:“MI:0915”(physical association)	0.560
VGLL3	CTRC	psi-mi:“MI:0915”(physical association)	0.560
CTRC	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
SPMIP9	CTRC	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	CTRC	psi-mi:“MI:0915”(physical association)	0.560
CTRC	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	CTRC	psi-mi:“MI:0915”(physical association)	0.560
CTRC	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
CTRC	MDFI	psi-mi:“MI:0915”(physical association)	0.000
CTRC	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
CTRC	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
CTRC	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
CTRC	GIPC2	psi-mi:“MI:0915”(physical association)	0.000
CTRC	KRT34	psi-mi:“MI:0915”(physical association)	0.000
CTRC	VGLL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): UBC (Biochemical Activity), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), SUMF1 (Affinity Capture-MS), SUMF1 (Affinity Capture-MS), CTRC (Two-hybrid), CTRC (Two-hybrid), CTRC (Two-hybrid), NFKBID (Two-hybrid), TEX37 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), VGLL3 (Two-hybrid)

ESM2 similar proteins: A0A126GUP6, A0A1S4H5M5, A0A6J1W8N1, B5U2W0, F5HKX0, O19023, O46644, O97366, P00772, P00773, P00774, P05208, P05805, P06871, P06872, P07477, P07478, P08217, P08218, P08419, P08861, P09093, P13582, P16049, P21902, P47796, P55091, P80009, P80010, Q29461, Q2VG86, Q3SYP2, Q49QW1, Q5R1M5, Q7M3E1, Q7M4I3, Q7PEV7, Q7QBP4, Q867B0, Q8I6K0

Diamond homologs: A0A182C2Z2, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	7
Uncertain significance	411
Likely benign	247
Benign	20

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
132150	NM_007272.3(CTRC):c.738_761del (p.Lys247_Arg254del)	Pathogenic
1734740	NM_007272.3(CTRC):c.376A>T (p.Lys126Ter)	Pathogenic
1749479	NM_007272.3(CTRC):c.576_588del (p.Trp191_Trp192insTer)	Pathogenic
1749750	NM_007272.3(CTRC):c.57dup (p.Pro20fs)	Pathogenic
1777451	NM_007272.3(CTRC):c.165G>A (p.Trp55Ter)	Pathogenic
1782301	NM_007272.3(CTRC):c.190_193del (p.Ile64fs)	Pathogenic
3226059	NM_007272.3(CTRC):c.246C>A (p.Tyr82Ter)	Pathogenic
528777	NC_000001.10:g.(?15764955)(15773090_?)del	Pathogenic
1752584	NM_007272.3(CTRC):c.627dup (p.Ser210fs)	Likely pathogenic
1798675	NM_007272.3(CTRC):c.2T>C (p.Met1Thr)	Likely pathogenic
2428696	NM_007272.3(CTRC):c.464G>A (p.Cys155Tyr)	Likely pathogenic
2626263	NM_007272.3(CTRC):c.129G>A (p.Trp43Ter)	Likely pathogenic
3766703	NM_007272.3(CTRC):c.429_430delinsTGGC (p.Glu144fs)	Likely pathogenic
523496	NM_007272.3(CTRC):c.699_703del (p.Ile234fs)	Likely pathogenic
580906	NM_007272.3(CTRC):c.133-1G>T	Likely pathogenic

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
1:15440298:A:AG	acceptor_gain	1.0000
1:15440299:G:GA	acceptor_gain	1.0000
1:15440391:GGTA:G	donor_loss	1.0000
1:15440392:GT:G	donor_loss	1.0000
1:15440393:T:G	donor_loss	1.0000
1:15442440:T:TA	acceptor_gain	1.0000
1:15442444:CAG:C	acceptor_loss	1.0000
1:15442445:A:AG	acceptor_gain	1.0000
1:15442445:A:T	acceptor_loss	1.0000
1:15442446:G:GC	acceptor_gain	1.0000
1:15442446:GC:G	acceptor_gain	1.0000
1:15442446:GCA:G	acceptor_gain	1.0000
1:15442446:GCAA:G	acceptor_gain	1.0000
1:15442446:GCAAC:G	acceptor_gain	1.0000
1:15442449:A:G	acceptor_gain	1.0000
1:15442570:GCG:G	donor_gain	1.0000
1:15442570:GCGGT:G	donor_loss	1.0000
1:15442571:CGGTG:C	donor_loss	1.0000
1:15442573:G:C	donor_loss	1.0000
1:15442573:G:GG	donor_gain	1.0000
1:15442574:T:G	donor_loss	1.0000
1:15443417:A:AG	acceptor_gain	1.0000
1:15443418:G:GA	acceptor_gain	1.0000
1:15443418:GC:G	acceptor_gain	1.0000
1:15443418:GCA:G	acceptor_gain	1.0000
1:15443418:GCAAT:G	acceptor_gain	1.0000
1:15443553:GGA:G	donor_gain	1.0000
1:15443554:GA:G	donor_gain	1.0000
1:15443554:GAG:G	donor_gain	1.0000
1:15443556:G:GG	donor_gain	1.0000

AlphaMissense

1749 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:15443542:G:C	W160C	0.999
1:15443542:G:T	W160C	0.999
1:15443424:A:T	D121V	0.998
1:15440388:G:C	W43C	0.997
1:15440388:G:T	W43C	0.997
1:15443424:A:C	D121A	0.997
1:15444716:T:A	C202S	0.997
1:15444717:G:C	C202S	0.997
1:15445740:G:C	W261C	0.997
1:15445740:G:T	W261C	0.997
1:15440386:T:A	W43R	0.996
1:15440386:T:C	W43R	0.996
1:15443429:G:C	A123P	0.996
1:15443540:T:A	W160R	0.996
1:15443540:T:C	W160R	0.996
1:15445601:A:T	D215V	0.996
1:15445601:A:C	D215A	0.995
1:15445644:G:C	W229C	0.995
1:15445644:G:T	W229C	0.995
1:15440536:G:A	C59Y	0.994
1:15440584:G:A	C75Y	0.994
1:15440585:C:G	C75W	0.994
1:15443423:G:C	D121H	0.994
1:15443424:A:G	D121G	0.994
1:15443425:T:A	D121E	0.994
1:15443425:T:G	D121E	0.994
1:15443430:C:A	A123D	0.994
1:15443527:C:G	C155W	0.994
1:15443543:G:T	G161C	0.994
1:15444668:T:A	C186S	0.994

dbSNP variants (sampled 300 via entrez): RS1000357867 (1:15441467 G>A), RS1001052445 (1:15440948 C>G,T), RS1001398008 (1:15446954 C>T), RS1001422689 (1:15447386 T>C,G), RS1001763538 (1:15436459 T>A), RS1001791784 (1:15447108 G>A), RS1001847755 (1:15447230 C>G,T), RS1002224359 (1:15440511 A>G), RS1002235704 (1:15443127 C>T), RS1002394688 (1:15448323 C>T), RS1002484166 (1:15437404 T>C), RS1002836008 (1:15448577 A>C), RS1003207935 (1:15444110 G>A), RS1003279758 (1:15439525 G>T), RS1003405411 (1:15444466 G>A)

Disease associations

OMIM: gene MIM:601405 | disease phenotypes: MIM:167800

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary chronic pancreatitis	Definitive	Autosomal dominant

Mondo (2): hereditary chronic pancreatitis (MONDO:0008185), chronic pancreatitis (MONDO:0005003)

Orphanet (1): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000819	Diabetes mellitus
HP:0000952	Jaundice
HP:0001733	Pancreatitis
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0001977	Abnormal thrombosis
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002570	Steatorrhea
HP:0004395	Malnutrition
HP:0005206	Pancreatic pseudocyst
HP:0005213	Pancreatic calcification
HP:0005236	Chronic calcifying pancreatitis
HP:0006725	Pancreatic adenocarcinoma
HP:0008205	Insulin-dependent but ketosis-resistant diabetes
HP:0009800	Maternal diabetes
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0030247	Splanchnic vein thrombosis
HP:0030992	Abnormal pancreatic duct morphology
HP:0100027	Recurrent pancreatitis
HP:0410019	Epigastric pain

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004860_132	Alcoholic chronic pancreatitis	2.000000e-10
GCST004860_133	Alcoholic chronic pancreatitis	8.000000e-09
GCST004860_18	Alcoholic chronic pancreatitis	1.000000e-07
GCST004860_43	Alcoholic chronic pancreatitis	3.000000e-22
GCST004860_47	Alcoholic chronic pancreatitis	3.000000e-06
GCST004860_67	Alcoholic chronic pancreatitis	8.000000e-10
GCST004860_68	Alcoholic chronic pancreatitis	2.000000e-07
GCST004860_69	Alcoholic chronic pancreatitis	6.000000e-07
GCST004860_81	Alcoholic chronic pancreatitis	1.000000e-16
GCST004860_94	Alcoholic chronic pancreatitis	1.000000e-11

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D050500	Pancreatitis, Chronic	C06.689.750.830; C23.550.291.500.750
C537262	Hereditary pancreatitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2386 (SINGLE PROTEIN), CHEMBL4523987 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 74,760 (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
CHEMBL50	QUERCETIN	3	74,559
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL1160008	IODOPHTHALEIN	2	67

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
milvexian	Inhibition	7.46	pKi
compound 20 [PMID: 12372533]	Inhibition	7.3	pKi

Binding affinities (BindingDB)

16 measured of 30 human assays (56 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(2,4-dimethoxyphenyl)-6,7-dimethoxy-3,1-benzoxazin-4-one	KI	100 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-methylsulfonylphenyl)-7,8-dihydro-[1,4]dioxino[2,3-g][3,1]benzoxazin-4-one	KI	200 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-chlorophenyl)-7,8-dihydro-[1,4]dioxino[2,3-g][3,1]benzoxazin-4-one	KI	400 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-methylsulfonylphenyl)-8,9-dihydro-7H-[1,4]dioxepino[2,3-g][3,1]benzoxazin-4-one	KI	500 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(4,6-dimethoxycyclohexa-1,3-dien-1-yl)-7,8-dihydro-[1,4]dioxino[2,3-g][3,1]benzoxazin-4-one	KI	500 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2,4-dimethoxyphenyl)-8,9-dihydro-7H-[1,4]dioxepino[2,3-g][3,1]benzoxazin-4-one	KI	600 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-methoxyphenyl)-8,9-dihydro-7H-[1,4]dioxepino[2,3-g][3,1]benzoxazin-4-one	KI	700 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
6,7-dimethoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one	KI	700 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-methoxyphenyl)-7,8-dihydro-[1,4]dioxino[2,3-g][3,1]benzoxazin-4-one	KI	700 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2,4-dimethoxyphenyl)-6-ethoxy-7-methoxy-3,1-benzoxazin-4-one	KI	1100 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
6-ethoxy-7-methoxy-2-(2-methoxyphenyl)-3,1-benzoxazin-4-one	KI	1200 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-methylsulfanylphenyl)-8,9-dihydro-7H-[1,4]dioxepino[2,3-g][3,1]benzoxazin-4-one	KI	1300 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-chlorophenyl)-8,9-dihydro-7H-[1,4]dioxepino[2,3-g][3,1]benzoxazin-4-one	KI	1900 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
2-(2-Iodo-phenyl)-6,7-dimethoxy-benzo[d][1,3]oxazin-4-one	KI	1900 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
6-ethoxy-7-methoxy-2-(2-methylsulfonylphenyl)-3,1-benzoxazin-4-one	KI	2800 nM	US-9695194: Benzoxazinone derivatives for treatment of skin diseases
4-bromo-1-[(4-methoxyphenyl)carbonyl]-3,5-dimethyl-1H-pyrazole	IC50	2840 nM

ChEMBL bioactivities

99 potent at pChembl≥5 of 158 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.38	Ki	0.42	nM	CHEMBL4450993
9.16	IC50	0.69	nM	CHEMBL47394
9.06	Ki	0.88	nM	CHEMBL4586444
8.82	Ki	1.5	nM	CHEMBL4469390
8.62	IC50	2.4	nM	CHEMBL296771
8.15	IC50	7	nM	CHEMBL102115
8.03	Ki	9.36	nM	CHYMOSTATIN
7.96	Ki	11	nM	CHEMBL4590739
7.90	Ki	12.6	nM	CHEMBL26494
7.70	Ki	20	nM	CHEMBL4638245
7.47	Ki	34	nM	CHEMBL355430
7.46	Ki	35	nM	MILVEXIAN
7.43	IC50	37	nM	CHEMBL100672
7.30	IC50	50	nM	CHEMBL107656
7.26	Ki	55	nM	CHEMBL11391
7.19	IC50	65	nM	CHEMBL320814
7.16	IC50	70	nM	CHEMBL108189
7.16	IC50	70	nM	CHEMBL457155
7.12	IC50	75	nM	CHEMBL109434
6.96	Ki	109	nM	CHEMBL283786
6.83	Ki	147	nM	CHEMBL26182
6.83	Ki	149	nM	CHEMBL79463
6.82	Ki	150	nM	CHEMBL4592765
6.80	IC50	160	nM	CHEMBL76522
6.77	Ki	171	nM	CHEMBL23910
6.75	Ki	177	nM	CHEMBL284017
6.70	Ki	200	nM	CHEMBL5808246
6.62	Ki	240	nM	CHEMBL275228
6.57	Ki	270	nM	CHEMBL274455
6.55	IC50	280	nM	CHEMBL322933
6.55	Ki	282	nM	CHEMBL284138
6.53	Ki	295	nM	CHEMBL26333
6.52	IC50	300	nM	CHEMBL331243
6.52	IC50	300	nM	CHEMBL322110
6.51	Ki	306	nM	CHEMBL284005
6.48	Ki	330	nM	CHEMBL4560112
6.46	Ki	348	nM	CHEMBL26496
6.44	Ki	364	nM	CHEMBL169707
6.44	Ki	364	nM	CHEMBL287318
6.42	IC50	380	nM	CHEMBL432978
6.42	IC50	380	nM	CHEMBL5425314
6.40	Ki	400	nM	CHEMBL5944124
6.38	IC50	420	nM	CHEMBL111765
6.35	Ki	451	nM	CHEMBL24697
6.34	Ki	455	nM	CHEMBL280377
6.34	Ki	458	nM	CHEMBL24734
6.33	Ki	463	nM	CHEMBL4560512
6.32	Ki	476	nM	CHEMBL433799
6.30	Ki	500	nM	CHEMBL113261
6.22	Ki	600	nM	CHEMBL6003452

PubChem BioAssay actives

117 with measured affinity, of 545 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)-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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0004	uM
1,3-dibenzyl-1,3-diazetidine-2,4-dione	219108: Compound was evaluated for its inhibitory activity against bovine pancreatic alpha-chymotrypsin	ic50	0.0007	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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0009	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-34,49-dibenzyl-4-[(2S)-butan-2-yl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-28-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-19-[(4-phenylphenyl)methyl]-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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0015	uM
1,3-bis(4-methylphenyl)-1,3-diazetidine-2,4-dione	219108: Compound was evaluated for its inhibitory activity against bovine pancreatic alpha-chymotrypsin	ic50	0.0024	uM
(3S,3aR,6aS)-3-prop-2-enyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	52606: Compound was evaluated for the inhibition of Chymotrypsinogen	ic50	0.0070	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	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.0094	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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0110	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.0126	uM
methyl 2-(4-chlorobenzoyl)pyrazole-3-carboxylate	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.0150	uM
(4-bromopyrazol-1-yl)-(4-methylphenyl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.0150	uM
methyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	1657784: Inhibition of human chymotrypsin by spectrophotometry	ki	0.0200	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	52472: Compound was evaluated for inhibitory activity against Bovine Chymotrypsinogen	ki	0.0340	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxopyrimidin-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817717: Binding affinity to human chymotrypsin assessed as inhibition constant using 3-Carbomethoxypropionyl-L-arginyl-Lprolyl-L-tyrosine p-Nitroaniline as substrate measured upto 120 mins by spectrophotometric analysis	ki	0.0350	uM
(3R,3aR,6aS)-3-prop-2-enyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	52606: Compound was evaluated for the inhibition of Chymotrypsinogen	ic50	0.0370	uM
(4-chloropyrazol-1-yl)-(4-fluorophenyl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.0400	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[(2R)-2-[[(1R)-3-(4-fluorophenyl)-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]propyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.0500	uM
(3-methylpyrazol-1-yl)-(3,4,5-trimethoxyphenyl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.0500	uM
benzyl N-[2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)amino]ethyl]-6-phenyl-3-pyridinyl]carbamate	52477: Tested for inhibitory activity against bovine pancreatic chymotrypsinogen	ki	0.0550	uM
1-benzoyl-N-phenylpyrazole-3-carboxamide	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.0570	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[(2R)-2-[[(1R)-3-(4-chlorophenyl)-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]propyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.0650	uM
(2S,4S,7R,8S,9S,12R,13R,16R,19S,20R)-2,9,13,19-tetramethyl-7-(4-methyl-2-oxopent-3-enyl)-5,17-dioxahexacyclo[10.10.0.02,9.04,8.013,20.016,19]docos-1(22)-ene-6,18-dione	52606: Compound was evaluated for the inhibition of Chymotrypsinogen	ic50	0.0700	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-oxo-1-[(2R)-2-[[(1R)-2-phenyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethyl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.0700	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-oxo-1-[(2R)-2-[[(1R)-3-phenyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]propyl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.0750	uM
4-[[2-[5-amino-2-(3-methoxyphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.1090	uM
[3-(2,4-dimethylbenzoyl)pyrazol-1-yl]-(4-fluorophenyl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.1200	uM
(3,4-dichlorophenyl)-pyrazol-1-ylmethanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.1250	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	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.1470	uM
methyl N-[(2S)-3-methyl-1-oxo-1-[(2S)-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamate	52607: Binding affinity for human pancreatic Chymotrypsinogen	ki	0.1490	uM
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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.1500	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	219110: The compound was evaluated for the inhibitory activity against alpha-chymotrypsin	ic50	0.1600	uM
4-[[2-(5-amino-6-oxo-2-pyridin-3-ylpyrimidin-1-yl)acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.1710	uM
4-[[2-(5-amino-6-oxo-2-phenylpyrimidin-1-yl)acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.1770	uM
(4-methylphenyl)-(3-nitropyrazol-1-yl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.1900	uM
4-[[2-(5-amino-6-oxo-2-pyridin-4-ylpyrimidin-1-yl)acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.2400	uM
(2-methylphenyl)-(4-nitropyrazol-1-yl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.2400	uM
6-chloro-3-phenylpyran-2-one	219114: In vitro binding affinity towards alpha-chymotrypsin from bovine pancreas.	ki	0.2700	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-[(2R)-2-[[(1R)-5-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexyl]carbamoyl]pyrrolidin-1-yl]-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.2800	uM
4-[[4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-3-oxo-5-phenylpentanoyl]amino]benzoic acid	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.2820	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-[3-(diethylamino)-3-oxopropyl]-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.2950	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-[(2R)-2-[[(1R)-4-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.3000	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3R)-1-amino-1,2-dioxoheptan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-(2-methylphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-3-carboxy-2-(3-carboxypropanoylamino)propanoyl]amino]-5-oxopentanoic acid	200537: Compound was tested for inhibition of Serine protease chymotrypsin	ic50	0.3000	uM
4-[[2-[5-amino-2-(3-fluorophenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-N-benzyl-2,2-difluoro-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.3060	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	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.3300	uM
(4-chloropyrazol-1-yl)-(3-nitrophenyl)methanone	1798347: Human Neutrophil Elastase Inhibition Assay from Article 10.1021/jm070600+: “N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase.”	ic50	0.3400	uM
4-[[2-[5-amino-2-(3-methylphenyl)-6-oxopyrimidin-1-yl]acetyl]amino]-2,2-difluoro-N-methyl-3-oxo-5-phenylpentanamide	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.3480	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	52474: In vitro inhibitory activity was determined against bovine pancreas chymotrypsin	ki	0.3640	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	52472: Compound was evaluated for inhibitory activity against Bovine Chymotrypsinogen	ki	0.3640	uM
3-[5-[(5-chlorothiophen-2-yl)methylamino]-1-(2,2-dimethylpropanoyl)pyrazol-3-yl]-1H-pyridin-2-one	2001900: Inhibition of chymotrypsin (unknown origin)	ic50	0.3800	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-oxo-1-[(2R)-2-[[(1R)-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexyl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]amino]-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	200533: Inhibitory concentration against Human pancreatic Serine protease chymotrypsin	ic50	0.3800	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
licochalcone B	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

125 unique, capped per target: 98 binding, 24 admet, 2 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4133523	Binding	Inhibition of human pancreas chymotrypsin C up to 0.78 mM using N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide as substrate pretreated for 5 mins followed by substrate addition measured after 30 mins by colorimetric method	Namalides B and C and Spumigins K-N from the Cultured Freshwater Cyanobacterium Sphaerospermopsis torques-reginae. — J Nat Prod
CHEMBL663108	Functional	Enzymatic stability was measured at 90 min incubation period	Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. — J Med Chem
CHEMBL4257233	ADMET	Stability of the compound assessed as chymotrypsin (unknown origin)-mediated compound hydrolysis at 250 uM by HPLC analysis	Peptides comprising non-natural amino acids and methods of making and using the same

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00956839	PHASE4	COMPLETED	Prospective Study of Efficacy of Intra-muscular Vitamin D3 in Tropical Calcific Pancreatitis
NCT00957151	PHASE4	COMPLETED	Evaluation of the Digestive and Metabolic Utilisation of Dietary Protein in Patients With Chronic Pancreatitis
NCT01430234	PHASE4	COMPLETED	Enzyme Suppletion in Exocrine Pancreatic Dysfunction
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT05069597	PHASE4	COMPLETED	Study to Evaluate Symptoms of Exocrine Pancreatic Insufficiency in Adult Participants With Cystic Fibrosis or Chronic Pancreatitis Treated With Creon
NCT06937294	PHASE4	RECRUITING	Metformin in Post Chronic Pancreatitis Diabetes Mellitus
NCT07285863	PHASE4	RECRUITING	A Study Of Effect Of Secretin For In Injection (Chirostim) On Pancreatic Fluid Composition In Healthy Subjects
NCT07418593	PHASE4	RECRUITING	Malabsorption Blood Test (MBT) to Determine Exocrine Pancreatic Function and Related Quality of Life in Chronic Pancreatitis
NCT00319358	PHASE3	COMPLETED	Role of Antioxidants Supplementation in Chronic Pancreatitis
NCT00414908	PHASE3	COMPLETED	A Study to Investigate the Effect of Delayed Release Pancrelipase on Maldigestion in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis and Pancreatectomy
NCT00559364	PHASE3	COMPLETED	Safety and Efficacy Study of Viokase® 16 for the Correction of Steatorrhea
NCT00658736	PHASE3	COMPLETED	Efficacy of EUS-guided Celiac Plexus Blockade in Chronic Pancreatitis
NCT00788593	PHASE3	COMPLETED	A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI)
NCT01318590	PHASE3	TERMINATED	Prospective Study on Endoscopic Ultrasound (EUS) Celiac Bloc Efficacy in Chronic Pancreatitis
NCT01731821	PHASE3	COMPLETED	Nonstented Stump-closed vs Duct-to-Mucosa Pancreaticojejunostomy After Pancreaticoduodenectomy
NCT00469703	PHASE2	TERMINATED	Safety and Efficacy Study of Thalomid in Patients With Chronic Pancreatitis
NCT00782795	PHASE2	COMPLETED	Chronic Pancreatitis. Effect of Pioglitazone on Endocrine Function, Exocrine Function & Structure, Pain & Life Quality
NCT01146561	PHASE2	TERMINATED	Safety And Efficacy Of Tanezumab In Patients With Chronic Pancreatitis
NCT01259544	PHASE2	COMPLETED	BreathID® Test: A Non-invasive Modality to Detect Pancreatic Exocrine Insufficiency
NCT01318369	PHASE2	COMPLETED	Efficacy Study of Δ9-THC to Treat Chronic Abdominal Pain
NCT01551511	PHASE2	COMPLETED	Δ9-THC (Namisol®) in Chronic Pancreatitis Patients Suffering From Persistent Abdominal Pain
NCT02849704	PHASE2	COMPLETED	Fat Malabsorption in Chronic Pancreatitis
NCT03283566	PHASE2	COMPLETED	Hydroxychloroquine and Metabolic Outcomes in Patients Undergoing TPAIT
NCT03481803	PHASE2	COMPLETED	A Phase IIa Study With Escalating Dose of MS1819-SD
NCT05906615	PHASE2	COMPLETED	Intravenous Lidocaine for Pain Associated With Pancreatic Cancer and Chronic Pancreatitis
NCT06230120	PHASE2	COMPLETED	Spinal Cord Stimulation for the Treatment of Pain in Chronic Pancreatitis
NCT06426160	PHASE2	RECRUITING	Tocilizumab for Painful Chronic Pancreatitis
NCT06729996	PHASE2	RECRUITING	Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis Associated Diabetes Mellitus
NCT07171112	PHASE2	RECRUITING	Smoking Cessation Trial in Recurrent Acute Pancreatitis and Chronic Pancreatitis
NCT00620919	PHASE1	TERMINATED	Secretin Enhanced Multidetector CT Pancreatography for Evaluation of Known or Suspected Chronic Pancreatitis
NCT00621283	PHASE1	TERMINATED	Secretin Enhanced MRCP for Evaluation of Pancreatic Duct in Pediatric Population
NCT00676702	PHASE1	COMPLETED	A Study of the Enzyme Activity and Safety of Pancrelipase in Patients With Severe Exocrine Pancreatic Insufficiency (EPI)
NCT01142128	PHASE1	TERMINATED	Viokase 16, Viokase16 Plus Nexium and Nexium Alone
NCT01159119	PHASE1	TERMINATED	A Study of EUR-1066 in Subjects With Chronic Pancreatitis, Exocrine Pancreatic Insufficiency and Chronic Abdominal Pain
NCT01452217	PHASE1	COMPLETED	Non-invasive MRI to Quantify the Effect of Secretin on Pancreatic Blood Flow and Perfusion in Healthy Volunteers
NCT02384018	PHASE1	COMPLETED	Mesenchymal Stem Cell and Islet Co-transplantation
NCT05095532	PHASE1	RECRUITING	Autologous Mesenchymal Stromal Cells and Islet Co-transplantation in TP-IAT
NCT05603702	PHASE1	RECRUITING	STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis