PRSS1

Summary

PRSS1 (serine protease 1, HGNC:9475) is a protein-coding gene on chromosome 7q34, encoding Serine protease 1 (P07477). Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec.

This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7.

Source: NCBI Gene 5644 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary chronic pancreatitis (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 51
• Clinical variants (ClinVar): 582 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9475
Approved symbol	PRSS1
Name	serine protease 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204983
Ensembl biotype	protein_coding
OMIM	276000
Entrez	5644

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 retained_intron

ENST00000311737, ENST00000463701, ENST00000485223, ENST00000486171, ENST00000492062, ENST00000497041

RefSeq mRNA: 1 — MANE Select: NM_002769 NM_002769

CCDS: CCDS5872

Canonical transcript exons

ENST00000311737 — 5 exons

Exon	Start	End
ENSE00002281116	142752868	142753072
ENSE00002446532	142751774	142752027
ENSE00002456924	142750555	142750714
ENSE00003491998	142752431	142752567
ENSE00004023530	142749472	142749524

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.7373 / max 3355.2595, expressed in 121 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81640	43.5792	35
81636	1.3834	83
81642	0.5676	4
81644	0.5506	4
81643	0.3399	4
81641	0.3367	4
81638	0.2951	21
81639	0.2254	20
81637	0.0385	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	100.00	gold quality
pancreas	UBERON:0001264	99.95	gold quality
islet of Langerhans	UBERON:0000006	99.85	gold quality
duodenum	UBERON:0002114	96.98	gold quality
body of stomach	UBERON:0001161	89.70	gold quality
fundus of stomach	UBERON:0001160	88.58	gold quality
ectocervix	UBERON:0012249	87.08	gold quality
right coronary artery	UBERON:0001625	86.09	gold quality
stomach	UBERON:0000945	85.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.33	gold quality
left uterine tube	UBERON:0001303	84.99	gold quality
right lobe of liver	UBERON:0001114	84.83	gold quality
endocervix	UBERON:0000458	84.46	gold quality
lower esophagus mucosa	UBERON:0035834	83.57	gold quality
right uterine tube	UBERON:0001302	83.00	gold quality
right adrenal gland	UBERON:0001233	82.79	gold quality
descending thoracic aorta	UBERON:0002345	82.18	gold quality
metanephros cortex	UBERON:0010533	80.99	gold quality
esophagus mucosa	UBERON:0002469	80.98	gold quality
transverse colon	UBERON:0001157	80.41	gold quality
right adrenal gland cortex	UBERON:0035827	79.85	gold quality
small intestine	UBERON:0002108	79.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.12	gold quality
placenta	UBERON:0001987	78.65	gold quality
left adrenal gland	UBERON:0001234	77.85	gold quality
spleen	UBERON:0002106	77.85	gold quality
uterine cervix	UBERON:0000002	77.79	gold quality
right ovary	UBERON:0002118	77.20	gold quality
left adrenal gland cortex	UBERON:0035825	76.58	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	73831.45
E-MTAB-5061	yes	56658.67
E-ENAD-27	yes	22386.15
E-GEOD-83139	yes	11409.05
E-HCAD-31	yes	4.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Reviews aspects of the molecular evolution and normal physiology of trypsinogen revealed by studies of PRSS1 in pancreatitis, and proposes three defensive mechanisms against premature trypsin activation within the pancreas. (PMID:11702203)
• This study reports a new pancreatitis-associated mutation–R116C (CGT > TGT: c.346C > T)–in the gene. (PMID:11708864)
• Here we report a family with hereditary pancreatitis that carries a novel PRSS1 mutation (R122C). (PMID:11719509)
• Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis (PMID:11932257)
• No difference was observed in the frequency of PRSS1 or PSTI polymorphisms in neonates carrying or not carrying CF mutations. (PMID:12529713)
• “Loss of function” mutations in the cationic trypsinogen gene may act as a protective factor against pancreatitis (PMID:12765848)
• This paper proposed that while “gain of function” mutations in the PRSS1 gene predispose one to pancreatitis, “loss of function” mutations in the gene may protect one against the disease. (PMID:12765848)
• trypsin plays a role in the growth of PAR-2-positive pancreatic cancer cells and serves as a potent mitogen in vitro, functioning as a growth factor (PMID:12792776)
• No mutation was found in the PRSS1 gene among pancreatitis Brazilian patients. (PMID:14526128)
• pancreatitis-associated cationic trypsin mutations causes increased transactivation of anionic trypsinogen. (PMID:14695529)
• Protease serine 1 (PRSS1) gene mutation is an important casuative factor in patients with hereditary pancreatitis. (PMID:15017610)
• Expression of trypsinogen 1 and 2 is better preserved than prostate specific antigen in high-grade prostatic neoplasms (PMID:15651064)
• Trypsin activates p42,44 MAP kinase phosphorylation via protein kinase C(epsilon)and proteinase activated receptor 2 in human cultured prostate stromal cells. This may be an important mechanism of BPH pathophysiology. (PMID:15678497)
• family of hereditary pancreatitis associated with the CT gene mutation, an arginine to histidine amino acid substitution at residue 122 (PMID:15725718)
• the risk of pancreatic cancer is not related to PRSS1 mutation type and does not appear to be related to the mode of inheritance (PMID:15749231)
• gene conversion between PRSS1 and PRSS2 trypsinogen genes can occur and cause genetically determined chronic pancreatitis (PMID:15776435)
• Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene. (PMID:15786540)
• study suggested a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression (PMID:16327984)
• Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. (PMID:16534247)
• Immunoreactive TAP in urine in acute pancreatitis is mainly composed of the C-terminal pentapeptide, DDDDK. (PMID:16685108)
• Genetic mutation in the pancreatic secretory trypsin inhibitor has been described to play a role in the development of pancreatitis. (PMID:16764792)
• protease serine 1 protease(PRSS1) defects seem to be causative for pancreatitis, whereas defects in protease serine 1 protease(SPINK1) are suggested to be associated with the disease (PMID:16954950)
• Mutations and variations in pancreatitis patients. (PMID:17003641)
• R122H human cationic trypsinogen transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. (PMID:17069643)
• Human cationic trypsinogen is sulfated on Tyr154. (PMID:17087724)
• Isoform B of trypsinogen 4, with a leucine N terminus, is the predominant (if not exclusive) form of the enzyme in post mortem human brain, but that both isoforms are expressed in transiently transfected cells (PMID:17480209)
• the mutation of PRSS1 gene, may not confer a high risk for recurrent pancreatitis. (PMID:17489851)
• in the investigated Finnish pedigree with hereditary pancreatitis, the PRSS1 mutation R122H is linked with chronic disease; although the SPINK1 mutation (N34S) was also observed in two individuals, it was not linked with the disease (PMID:17613931)
• Hereditary pancreatitis is associated with R122H mutation in exon 3 of PRSS1 gene. (PMID:17641559)
• Patients with HP have a marked relative and absolute increased risk of PA as compared to the general population, especially in smokers. There is no correlation with the type of PRSS1 mutation. (PMID:18184119)
• Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis. (PMID:18272034)
• Total immunoreactivity of soluble urinary MMP-14 and the levels of trypsin (TRY)-1 and TRY-2, but not of TATI, were also significantly increased in diabetic nephropathy (PMID:18428024)
• A fusion with PRSS2 is associated with hereditary pancreatitis. (PMID:18461367)
• study reports a novel A121T mutation; this novel PRSS1 A121T mutation highlights the surface exposed region PRSS1 A121-R122-V123 as a hotspot for hereditary pancreatitis (PMID:18511571)
• Multisite mutations of PRSS1 were found in a patient with chronic pancreatitis. C to A mutation occurred in exon 3 of PRSS1, and T to A mutation in the same exon. (PMID:18522894)
• Benign pancreatic hyperenzymemia cannot be explained by mutations in PRSS1. (PMID:18580441)
• In members from 10 unrelated HP families (all R122H-positive), we found 7 different haplotypes to segregate with the R122H mutation. (PMID:18702646)
• PRSS1 and SPINK1 mutations were not rare in Korean patients with idiopathic and familial pancreatitis. SPINK1 IVS3+2T>C was a prevalent mutation in this population. (PMID:18852684)
• Hereditary pancreatitis patients with the different mutations in the PRSS1 gene had similar histopathological features and the same clinical outcome. (PMID:18946221)
• The mutation spectrum of PRSS1 and SPNK1 genes in chinese subjects is different from that in western countries. (PMID:19433603)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	prss1	ENSDARG00000042993
mus_musculus	Try5	ENSMUSG00000036938
mus_musculus	Try4	ENSMUSG00000054106
mus_musculus	Prss2	ENSMUSG00000057163
mus_musculus	Prss1l	ENSMUSG00000058119
mus_musculus	Prss1	ENSMUSG00000062751
mus_musculus	Prss3l	ENSMUSG00000071517
mus_musculus	Prss3	ENSMUSG00000071519
mus_musculus	Try10	ENSMUSG00000071521
rattus_norvegicus	Prss2l1	ENSRNOG00000050493
rattus_norvegicus	Prss1	ENSRNOG00000063605
rattus_norvegicus	Prss2	ENSRNOG00000064731
rattus_norvegicus	Try10	ENSRNOG00000070336
rattus_norvegicus		ENSRNOG00000075892
rattus_norvegicus	Prss3	ENSRNOG00000078399
rattus_norvegicus		ENSRNOG00000089144

Paralogs (3): PRSS3 (ENSG00000010438), PLAU (ENSG00000122861), PRSS2 (ENSG00000275896)

Protein

Protein identifiers

Serine protease 1 — P07477 (reviewed: P07477)

Alternative names: Anionic trypsin I, Anionic trypsin-I, Beta-trypsin, Cationic trypsinogen, Pretrypsinogen I, Trypsin I, Trypsin-1

All UniProt accessions (3): P07477, E7EQ64, H0Y8D1

UniProt curated annotations — full annotation on UniProt →

Function. Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.

Subunit / interactions. Interacts with SERPINA1.

Subcellular location. Secreted. Extracellular space.

Post-translational modifications. Occurs in a single-chain form and a two-chain form, produced by proteolytic cleavage after Arg-122. Sulfation at Tyr-154 increases selectivity towards basic versus apolar residues at the P2’ position of inhibitors that bind in a substrate-like fashion. Although the increase in selectivity is relatively small, it may facilitate digestion of a broader range of dietary proteins.

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.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_002760* (*=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
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00089

UniProt features (57 total): strand 16, sequence variant 13, disulfide bond 5, binding site 4, helix 4, chain 3, active site 3, turn 2, signal peptide 1, propeptide 1, site 1, modified residue 1, mutagenesis site 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
2RA3	X-RAY DIFFRACTION	1.46
4WWY	X-RAY DIFFRACTION	1.7
4WXV	X-RAY DIFFRACTION	2.1
7QE9	X-RAY DIFFRACTION	2.1
1FXY	X-RAY DIFFRACTION	2.15
1TRN	X-RAY DIFFRACTION	2.2
8ZIY	ELECTRON MICROSCOPY	2.64
8ZJ4	ELECTRON MICROSCOPY	2.67
7QE8	X-RAY DIFFRACTION	2.9
8ZI4	ELECTRON MICROSCOPY	2.95
8ZIV	ELECTRON MICROSCOPY	2.95
8H3S	ELECTRON MICROSCOPY	4.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07477-F1	92.24	0.86

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 (4): 194 (required for specificity); 63 (charge relay system); 107 (charge relay system); 200 (charge relay system)

Ligand- & substrate-binding residues (4): 77; 80; 85; 75

Post-translational modifications (1): 154

Disulfide bonds (5): 30–160, 48–64, 139–206, 171–185, 196–220

Mutagenesis-validated functional residues (1):

Position	Phenotype
154	lack of sulfation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 107 (showing top): GOBP_DIGESTION, ENK_UV_RESPONSE_KERATINOCYTE_UP, CHANG_IMMORTALIZED_BY_HPV31_DN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GATA1_04, MODULE_165, DORSEY_GAB2_TARGETS, GOBP_EXTRACELLULAR_MATRIX_DISASSEMBLY, HAN_SATB1_TARGETS_DN, GOCC_BLOOD_MICROPARTICLE, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS, YOSHIMURA_MAPK8_TARGETS_UP, GATA_C

GO Biological Process (3): proteolysis (GO:0006508), digestion (GO:0007586), extracellular matrix disassembly (GO:0022617)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), metal ion binding (GO:0046872), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Degradation of the extracellular matrix	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
multicellular organismal process	1
cellular component disassembly	1
extracellular matrix organization	1
endopeptidase activity	1
serine-type peptidase activity	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
external encapsulating structure	1
extracellular region	1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS1	SPINK1	P00995	989
PRSS1	CFTR	P13569	854
PRSS1	PALB2	Q86YC2	754
PRSS1	MBL2	P11226	751
PRSS1	SERPINA1	P01009	745
PRSS1	CPA1	P15085	726
PRSS1	HTRA4	P83105	704
PRSS1	CTSB	P07858	644
PRSS1	PRSS58	Q8IYP2	631
PRSS1	A2M	P01023	624
PRSS1	PALLD	Q8WX93	601
PRSS1	BRCA2	P51587	595
PRSS1	FCN3	O75636	593
PRSS1	STK11	Q15831	584
PRSS1	CPB1	P15086	577

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
KDM6A	KMT2D	psi-mi:“MI:0914”(association)	0.530
GATA2	BANF1	psi-mi:“MI:0914”(association)	0.530
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
GRB2	PRSS1	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
CDY2A	SMPD2	psi-mi:“MI:0914”(association)	0.350
EPAS1	POLR2D	psi-mi:“MI:0914”(association)	0.350
FANCM	PRSS1	psi-mi:“MI:0914”(association)	0.350
NCAPG	SMC2	psi-mi:“MI:0914”(association)	0.350
PIWIL4	CSTA	psi-mi:“MI:0914”(association)	0.350
PRDM5	PRSS1	psi-mi:“MI:0914”(association)	0.350
PRMT3	CSTA	psi-mi:“MI:0914”(association)	0.350
RAD51	CSTA	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
EPHA3	FHAD1	psi-mi:“MI:0914”(association)	0.350
PRSS2	POTEF	psi-mi:“MI:0914”(association)	0.350
PRSS1	HSPA5	psi-mi:“MI:0914”(association)	0.350
CTNNA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
PPARA	PTGES	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
CTNNA1	KIF2A	psi-mi:“MI:0914”(association)	0.350
FOS	C11orf98	psi-mi:“MI:0914”(association)	0.350
ATF3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CASP3	C11orf98	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): PRSS1 (Affinity Capture-MS), PRSS1 (Co-fractionation), PRSS1 (Co-fractionation), PRSS1 (Co-fractionation), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS)

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

2 interactions.

A	Effect	B	Mechanism
PRSS1	“up-regulates activity”	F2RL1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Tie2 Signaling	5	75.1×	7e-07
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	64.9×	1e-06
Downstream signal transduction	5	47.6×	2e-06
DAP12 signaling	5	46.0×	2e-06
FCERI mediated MAPK activation	5	43.3×	2e-06
Signaling by FGFR2 in disease	5	33.2×	6e-06
Signaling by SCF-KIT	5	31.0×	7e-06
RAF/MAP kinase cascade	5	7.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	338
Likely benign	170
Benign	18

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
11882	NM_002769.5(PRSS1):c.365_366delinsAT (p.Arg122His)	Pathogenic
11883	NM_002769.5(PRSS1):c.364C>T (p.Arg122Cys)	Pathogenic
11884	PRSS1, TRIPLICATION	Pathogenic
132152	NP_002760.1(PRSS1):p.Cys139Ser	Pathogenic
1454580	NM_002769.5(PRSS1):c.116T>C (p.Val39Ala)	Pathogenic
267330	NC_000007.13:g.(?142457330)(142460424_?)dup	Pathogenic
583681	NC_000007.13:g.(?142457132)(142457395_?)dup	Pathogenic
973568	NC_000007.14:g.142749126_142753040dup	Pathogenic
1068176	NC_000007.13:g.(?142459615)(142460871_?)dup	Likely pathogenic
161986	NM_002769.5(PRSS1):c.347G>C (p.Arg116Pro)	Likely pathogenic
417552	NC_000007.13:g.(?142457319)(142460927_?)dup	Likely pathogenic
665642	NC_000007.13:g.(?142459615)(142460881_?)dup	Likely pathogenic
831511	NC_000007.14:g.(?142749147)(142753020_?)dup	Likely pathogenic

SpliceAI

631 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142750542:A:AG	acceptor_gain	1.0000
7:142750543:T:G	acceptor_gain	1.0000
7:142750548:A:AG	acceptor_gain	1.0000
7:142750550:TCCAG:T	acceptor_loss	1.0000
7:142750551:CCA:C	acceptor_loss	1.0000
7:142750552:CA:C	acceptor_loss	1.0000
7:142750553:A:AG	acceptor_gain	1.0000
7:142750553:AGTT:A	acceptor_gain	1.0000
7:142750554:G:GT	acceptor_gain	1.0000
7:142750554:GT:G	acceptor_gain	1.0000
7:142750554:GTT:G	acceptor_gain	1.0000
7:142750554:GTTG:G	acceptor_gain	1.0000
7:142750682:G:GG	donor_gain	1.0000
7:142750687:T:TA	donor_gain	1.0000
7:142750688:G:GA	donor_gain	1.0000
7:142750710:AAGTC:A	donor_gain	1.0000
7:142750712:GTC:G	donor_gain	1.0000
7:142750713:TC:T	donor_gain	1.0000
7:142750715:G:GG	donor_gain	1.0000
7:142751876:G:GT	donor_gain	1.0000
7:142752024:GGCG:G	donor_gain	1.0000
7:142752025:GCGG:G	donor_gain	1.0000
7:142752419:T:A	acceptor_gain	1.0000
7:142752481:GC:G	donor_gain	1.0000
7:142752482:C:G	donor_gain	1.0000
7:142752507:A:T	donor_gain	1.0000
7:142752865:CAGGG:C	acceptor_loss	1.0000
7:142752866:A:AG	acceptor_gain	1.0000
7:142752866:AG:A	acceptor_gain	1.0000
7:142752866:AGGGT:A	acceptor_gain	1.0000

AlphaMissense

1614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142751893:A:T	D107V	0.999
7:142752005:G:C	W144C	0.999
7:142752005:G:T	W144C	0.999
7:142752990:G:C	W238C	0.999
7:142752990:G:T	W238C	0.999
7:142751892:G:C	D107H	0.998
7:142751893:A:C	D107A	0.998
7:142752872:A:T	D199V	0.998
7:142750657:G:A	C48Y	0.997
7:142750683:T:A	W57R	0.997
7:142750683:T:C	W57R	0.997
7:142752003:T:A	W144R	0.997
7:142752003:T:C	W144R	0.997
7:142752487:T:A	C171S	0.997
7:142752488:G:C	C171S	0.997
7:142752529:T:A	C185S	0.997
7:142752530:G:A	C185Y	0.997
7:142752530:G:C	C185S	0.997
7:142752556:G:C	D194H	0.997
7:142752562:T:A	C196S	0.997
7:142752563:G:A	C196Y	0.997
7:142752563:G:C	C196S	0.997
7:142752871:G:C	D199H	0.997
7:142752872:A:C	D199A	0.997
7:142752878:G:T	G201V	0.997
7:142752988:T:A	W238R	0.997
7:142752988:T:C	W238R	0.997
7:142750685:G:C	W57C	0.996
7:142750685:G:T	W57C	0.996
7:142750705:G:A	C64Y	0.996

dbSNP variants (sampled 300 via entrez): RS1000067806 (7:142751622 A>C), RS1000539824 (7:142748938 A>G,T), RS1000645950 (7:142748002 G>A), RS1001013530 (7:142748786 C>G), RS1001325738 (7:142748224 C>T), RS1004296187 (7:142751346 G>A), RS1004452686 (7:142747580 T>G), RS1004529553 (7:142748230 C>T), RS1004595187 (7:142752191 G>A,C), RS1006257067 (7:142753523 C>G,T), RS1006643323 (7:142749025 T>C), RS1007641581 (7:142749601 C>T), RS1007974803 (7:142750482 A>G), RS1008683472 (7:142753163 A>C), RS1009305850 (7:142749229 A>G)

Disease associations

OMIM: gene MIM:276000 | disease phenotypes: MIM:167800, MIM:277440, MIM:614044

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary chronic pancreatitis	Definitive	Autosomal dominant
malignant pancreatic neoplasm	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary chronic pancreatitis	Definitive	AD

Mondo (6): hereditary chronic pancreatitis (MONDO:0008185), myoepithelial tumor (MONDO:0002380), vitamin D-dependent rickets, type 2A (MONDO:0010186), trypsinogen deficiency (MONDO:0013543), hereditary neoplastic syndrome (MONDO:0015356), malignant pancreatic neoplasm (MONDO:0009831)

Orphanet (3): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Hypocalcemic vitamin D-resistant rickets (Orphanet:93160), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

17 total (17 of 17 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:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0001977	Abnormal thrombosis
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002570	Steatorrhea
HP:0005206	Pancreatic pseudocyst
HP:0005213	Pancreatic calcification
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0030247	Splanchnic vein thrombosis
HP:0100027	Recurrent pancreatitis

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST001741_1	Pancreatitis	2.000000e-14
GCST004136_19	Methadone dose in opioid dependence	4.000000e-06
GCST004860_100	Alcoholic chronic pancreatitis	5.000000e-15
GCST004860_103	Alcoholic chronic pancreatitis	3.000000e-10
GCST004860_104	Alcoholic chronic pancreatitis	8.000000e-18
GCST004860_105	Alcoholic chronic pancreatitis	3.000000e-14
GCST004860_106	Alcoholic chronic pancreatitis	4.000000e-19
GCST004860_114	Alcoholic chronic pancreatitis	2.000000e-07
GCST004860_118	Alcoholic chronic pancreatitis	2.000000e-12
GCST004860_119	Alcoholic chronic pancreatitis	2.000000e-23
GCST004860_12	Alcoholic chronic pancreatitis	5.000000e-18
GCST004860_125	Alcoholic chronic pancreatitis	5.000000e-10
GCST004860_131	Alcoholic chronic pancreatitis	2.000000e-18
GCST004860_139	Alcoholic chronic pancreatitis	3.000000e-14
GCST004860_140	Alcoholic chronic pancreatitis	4.000000e-16
GCST004860_141	Alcoholic chronic pancreatitis	2.000000e-14
GCST004860_142	Alcoholic chronic pancreatitis	1.000000e-08
GCST004860_143	Alcoholic chronic pancreatitis	3.000000e-12
GCST004860_153	Alcoholic chronic pancreatitis	1.000000e-16
GCST004860_20	Alcoholic chronic pancreatitis	1.000000e-22
GCST004860_23	Alcoholic chronic pancreatitis	4.000000e-07
GCST004860_26	Alcoholic chronic pancreatitis	6.000000e-22
GCST004860_28	Alcoholic chronic pancreatitis	1.000000e-06
GCST004860_29	Alcoholic chronic pancreatitis	2.000000e-22
GCST004860_3	Alcoholic chronic pancreatitis	2.000000e-18
GCST004860_30	Alcoholic chronic pancreatitis	9.000000e-21
GCST004860_33	Alcoholic chronic pancreatitis	8.000000e-18
GCST004860_37	Alcoholic chronic pancreatitis	3.000000e-16
GCST004860_38	Alcoholic chronic pancreatitis	9.000000e-32
GCST004860_39	Alcoholic chronic pancreatitis	1.000000e-22

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007907	methadone dose measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C537262	Hereditary pancreatitis (supp.)
C562794	Vitamin D-Dependent Rickets, Type 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL209 (SINGLE PROTEIN), CHEMBL2095204 (PROTEIN FAMILY), CHEMBL2096988 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 182,539 (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
CHEMBL1166	ARGATROBAN	4	231
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL338802	SULFAGUANIDINE	4	4,956
CHEMBL5189739	BEROTRALSTAT	4	7
CHEMBL273264	NAFAMOSTAT	3	7,063
CHEMBL46618	OTAMIXABAN	3	526
CHEMBL590799	CAMOSTAT	3	6,733
CHEMBL85164	CAMOSTAT MESILATE	3	1,558
CHEMBL226335	RUTIN	3	57,988
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL48361	DABIGATRAN	3	13,443
CHEMBL50	QUERCETIN	3	74,559
CHEMBL9509	SILIBININ	3	130
CHEMBL273196	EFEGATRAN	2	1,037
CHEMBL114586	SEPIMOSTAT	2	156
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL3786896	AZD-8165	1	5

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
RWJ-56423	Inhibition	8.09	pKi
nafamostat	Inhibition	7.77	pIC50
compound 9 [PMID: 3514912]	Inhibition	7.71	pIC50
camostat	Inhibition	7.3	pIC50

Binding affinities (BindingDB)

463 measured of 507 human assays (507 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.075 nM
(2S)-2-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonyl-3-methylthiophen-2-yl]propanoylamino]butanedioic acid	KI	0.13 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]butanedioic acid	KI	0.14 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]cyclobutanecarbonyl]amino]butanedioic acid	KI	0.14 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[(4R)-3-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-1,3-thiazolidine-4-carbonyl]amino]butanedioic acid	KI	0.15 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-(4-hydroxyphenyl)propanoic acid	IC50	0.17 nM	US-9199927: Guanidinobenzoic acid compound
(2R)-3-[4-(carboxymethoxy)phenyl]-2-[[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]propanoic acid	IC50	0.18 nM	US-9199927: Guanidinobenzoic acid compound
3-[[carboxymethyl-[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]propanoyl]amino]methyl]benzoic acid	IC50	0.19 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-(4-chlorophenyl)propanoic acid	IC50	0.2 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-(4-carbamimidoyl-2-fluorophenoxy)carbonyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-6-carbonyl]amino]butanedioic acid	KI	0.2 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-chlorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]-3-sulfopropanoic acid	KI	0.21 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxy-2,6-difluorophenyl]acetyl]amino]-3-phenylpropanoic acid	IC50	0.21 nM	US-9199927: Guanidinobenzoic acid compound
4-[[carboxymethyl-[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]methyl]thiophene-2-carboxylic acid	IC50	0.21 nM	US-9199927: Guanidinobenzoic acid compound
2-[4-[(2S)-2-carboxy-2-[3-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]propanoylamino]ethyl]phenoxy]-2-methylpropanoic acid	IC50	0.22 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-(4-fluorophenyl)propanoic acid	IC50	0.23 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-(4-methoxyphenyl)propanoic acid	IC50	0.23 nM	US-9199927: Guanidinobenzoic acid compound
3-[[carboxymethyl-[[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]-methylcarbamoyl]amino]methyl]benzoic acid	IC50	0.23 nM	US-9199927: Guanidinobenzoic acid compound
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-prop-2-enylamino]acetic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
4-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]phthalic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
3-[[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]-3-phenylpropanoic acid	IC50	0.24 nM	US-9199927: Guanidinobenzoic acid compound
2-[4-[[carboxymethyl-[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]methyl]phenyl]acetic acid	IC50	0.24 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-(2H-tetrazol-5-yl)propanoic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[(2S)-1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-3-sulfopropanoic acid	KI	0.24 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2R)-2-[[(2R)-1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-3-sulfopropanoic acid	KI	0.24 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-(2H-tetrazol-5-yl)propanoic acid	KI	0.24 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.25 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.26 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
2-[[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]-2-phenylacetic acid	IC50	0.26 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2,6-dichloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-phenylpropanoic acid	IC50	0.26 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-(3-fluorophenyl)propanoic acid	IC50	0.26 nM	US-9199927: Guanidinobenzoic acid compound
(2R)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.26 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]-3-sulfopropanoic acid	KI	0.27 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]pentanedioic acid	KI	0.27 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
3-[[carboxymethyl-[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]methyl]benzoic acid	IC50	0.27 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]pentanedioic acid	KI	0.27 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.28 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
3-[5-(2-bromo-4-carbamimidoylphenoxy)carbonylthiophen-2-yl]-2-methylpropanoic acid	KI	0.29 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]acetic acid	KI	0.29 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
2-[4-[[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]phenyl]acetic acid	IC50	0.29 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxy-2-(trifluoromethyl)phenyl]acetyl]amino]-3-phenylpropanoic acid	IC50	0.29 nM	US-9199927: Guanidinobenzoic acid compound
(2S)-2-[[2-[2,3-dichloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-3-phenylpropanoic acid	IC50	0.29 nM	US-9199927: Guanidinobenzoic acid compound
2-[benzyl-[3-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]propanoyl]amino]acetic acid	IC50	0.29 nM	US-9199927: Guanidinobenzoic acid compound
4-[[[(1R)-1-carboxyethyl]-[6-[4-(diaminomethylideneamino)benzoyl]oxyquinoline-2-carbonyl]amino]methyl]thiophene-2-carboxylic acid	IC50	0.29 nM	US-9199927: Guanidinobenzoic acid compound
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]acetic acid	KI	0.29 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
2-[[3-[2-chloro-4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]propanoylamino]methyl]benzoic acid	IC50	0.3 nM	US-9199927: Guanidinobenzoic acid compound
(2S,4R)-1-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-4-hydroxypyrrolidine-2-carboxylic acid	KI	0.3 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S,4R)-1-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-4-hydroxypyrrolidine-2-carboxylic acid	KI	0.3 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
2-[[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]methyl]pentanedioic acid	KI	0.31 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]propanoylamino]butanedioic acid	KI	0.31 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
5-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]benzene-1,3-dicarboxylic acid	KI	0.31 nM	US-9227949: Heteroarylcarboxylic acid ester derivative

ChEMBL bioactivities

2264 potent at pChembl≥5 of 2518 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL100989
10.52	Ki	0.03	nM	CHEMBL3623792
10.52	Ki	0.03	nM	CHEMBL453539
10.35	Ki	0.045	nM	CHEMBL607008
10.35	Ki	0.045	nM	CHEMBL290376
10.27	Ki	0.054	nM	CHEMBL3642936
10.10	Ki	0.08	nM	CHEMBL3944540
10.00	Ki	0.1	nM	CHEMBL239127
10.00	Ki	0.1	nM	CHEMBL453539
9.96	Ki	0.11	nM	CHEMBL418071
9.92	Ki	0.12	nM	CHEMBL3642924
9.92	IC50	0.12	nM	CHEMBL99622
9.85	IC50	0.14	nM	CHEMBL3980104
9.85	IC50	0.14	nM	CHEMBL3917451
9.82	Ki	0.15	nM	CHEMBL3642903
9.80	Ki	0.16	nM	CHEMBL3623793
9.80	Ki	0.16	nM	CHEMBL4483694
9.77	IC50	0.17	nM	CHEMBL3951207
9.77	IC50	0.17	nM	CHEMBL3947949
9.77	IC50	0.17	nM	CHEMBL3985298
9.77	IC50	0.17	nM	CHEMBL3972244
9.77	IC50	0.17	nM	CHEMBL3909962
9.74	Ki	0.18	nM	CHEMBL3642902
9.74	Ki	0.18	nM	CHEMBL3642965
9.74	Ki	0.18	nM	CHEMBL3672886
9.74	IC50	0.18	nM	CHEMBL4109828
9.74	IC50	0.18	nM	CHEMBL3961130
9.72	Ki	0.19	nM	CHEMBL3642941
9.72	IC50	0.19	nM	CHEMBL3917451
9.72	IC50	0.19	nM	CHEMBL3951207
9.72	IC50	0.19	nM	CHEMBL3897484
9.72	IC50	0.19	nM	CHEMBL3939171
9.72	IC50	0.19	nM	CHEMBL3969953
9.72	Ki	0.19	nM	CHEMBL3914629
9.70	Ki	0.2	nM	CHEMBL3642932
9.70	Ki	0.2	nM	CHEMBL3642982
9.70	IC50	0.2	nM	CHEMBL3897484
9.70	IC50	0.2	nM	CHEMBL3977211
9.68	Ki	0.21	nM	CHEMBL3642957
9.68	Ki	0.21	nM	CHEMBL3672880
9.68	IC50	0.21	nM	CHEMBL3985298
9.68	IC50	0.21	nM	CHEMBL3917451
9.68	IC50	0.21	nM	CHEMBL3957994
9.68	IC50	0.21	nM	CHEMBL3940399
9.68	Ki	0.21	nM	CHEMBL3921980
9.66	Ki	0.22	nM	CHEMBL3642895
9.66	Ki	0.22	nM	CHEMBL3642958
9.66	IC50	0.22	nM	CHEMBL3979741
9.66	IC50	0.22	nM	CHEMBL3971081
9.64	Ki	0.23	nM	CHEMBL3642933

PubChem BioAssay actives

1688 with measured affinity, of 3998 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
(3S,3aS,6aS)-3-phenylsulfanyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	215376: Inhibition of trypsin	ic50	<0.0001	uM
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,41S,44S,50S)-50-benzyl-4,19-bis[(2S)-butan-2-yl]-25,34-bis[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,43,49,52-tetradecaoxo-54,55-dithia-2,5,11,17,20,23,26,29,32,35,38,42,48,51-tetradecazapentacyclo[29.21.4.07,11.013,17.044,48]hexapentacontane-41-carboxylic acid	1251573: Inhibition of beta-trypsin (unknown origin) using Bz-FVRpNA substrate by spectrophotometry method	ki	<0.0001	uM
[(1R)-1-[[(2S)-1-[(2R)-2-acetamido-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-4-(diaminomethylideneamino)butyl]boronic acid	215748: Binding affinity against Trypsin	ki	<0.0001	uM
2-[(1R,3aS,7S,10S,13S,16S,19S,22S,25R,28S,31S,34S,37S,40S,43R,49S,55S,58R,61S,64R,67S,73S,79S,82R,88S,94S,97S)-10,19,22-tris(4-aminobutyl)-73-(2-amino-2-oxoethyl)-13,61-bis[(2S)-butan-2-yl]-28,31,67-tris(3-carbamimidamidopropyl)-40,97-bis(carboxymethyl)-37,88,94-tris(hydroxymethyl)-79-[(4-hydroxyphenyl)methyl]-55-methyl-16-(2-methylpropyl)-1a,2,4a,8,11,14,17,20,23,26,29,32,35,38,41,44,50,53,56,59,62,65,68,71,74,77,80,83,86,89,92,95,98-tritriacontaoxo-3a-propan-2-yl-7a,8a,11a,12a,15a,16a-hexathia-2a,3,5a,9,12,15,18,21,24,27,30,33,36,39,42,45,51,54,57,60,63,66,69,72,75,78,81,84,87,90,93,96,99-tritriacontazahexacyclo[56.47.4.425,64.443,82.03,7.045,49]heptadecahectan-34-yl]acetic acid	1533293: Inhibition of trypsin (unknown origin)	ki	<0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-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-40-yl]acetic acid	1361038: Inhibition of human cationic trypsin using Boc-VPR-MCA as substrate measured every 30 secs for 10 mins	ki	<0.0001	uM
(3R,3aS,6aS)-3-phenylsulfanyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	215376: Inhibition of trypsin	ic50	0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43R,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-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-40-yl]acetic acid	218709: Compound was tested for inhibition of Sunflower beta-trypsin	ki	0.0001	uM
N-[(6-amino-2-methyl-3-pyridinyl)methyl]-2-[(3R)-3,6-dimethyl-3-(2-methylpropyl)-2,8-dioxo-1,4-dihydro-1,7-naphthyridin-7-yl]acetamide	211749: The compound was tested for its ability to inhibit thrombin.	ki	0.0002	uM
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,41S,44S,50S)-50-benzyl-4-[(2S)-butan-2-yl]-25,34-bis[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,43,49,52-tetradecaoxo-54,55-dithia-2,5,11,17,20,23,26,29,32,35,38,42,48,51-tetradecazapentacyclo[29.21.4.07,11.013,17.044,48]hexapentacontane-41-carboxylic acid	1251573: Inhibition of beta-trypsin (unknown origin) using Bz-FVRpNA substrate by spectrophotometry method	ki	0.0002	uM
(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[2-[[(1S,6S,12S,15S,18S,21S,24S,27S,30R,33S,36S,39S,42S,45S,48R,53S,56S,62S,68S,71R,74S,79S,85S)-6-[[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-methylbutanoyl]amino]-15,24,27-tris(4-aminobutyl)-62-(2-amino-2-oxoethyl)-18,74-bis[(2S)-butan-2-yl]-33,36,68-tris(3-carbamimidamidopropyl)-39,45-bis(carboxymethyl)-42-(hydroxymethyl)-56-[(4-hydroxyphenyl)methyl]-79-methyl-21-(2-methylpropyl)-7,13,16,19,22,25,28,31,34,37,40,43,46,55,58,61,64,67,70,73,76,78,81,84,90-pentacosaoxo-3,4,50,51,92,93-hexathia-8,14,17,20,23,26,29,32,35,38,41,44,47,54,57,60,63,66,69,72,75,77,80,83,89-pentacosazapentacyclo[46.28.14.430,71.08,12.085,89]tetranonacontane-53-carbonyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]butanedioic acid	1628817: Inhibition of trypsin (unknown origin) using Bz-FVRpNA as substrate incubated for 30 mins measured for 7 mins by morrison plot analysis	ki	0.0002	uM
N-[(6-amino-2-methyl-3-pyridinyl)methyl]-2-[6-methyl-3,3-bis(2-methylpropyl)-2,8-dioxo-1,4-dihydro-1,7-naphthyridin-7-yl]acetamide	211749: The compound was tested for its ability to inhibit thrombin.	ki	0.0003	uM
N-[7-amino-1-[2-(4-carbamoylphenyl)ethylamino]-1,2-dioxoheptan-3-yl]-2-(4-methoxyphenyl)-8-(2-methylpropyl)-1,3-dioxo-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxamide	215752: Compound was evaluated for its binding affinity to the trypsin enzyme	ki	0.0003	uM
2-[[(2S)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	766527: Inhibition of human trypsin	ki	0.0003	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	215245: In vitro inhibition constant (Ki) against human trypsin was determined	ki	0.0003	uM
N-[7-amino-1-[2-(4-carbamoylphenyl)ethylamino]-1,2-dioxoheptan-3-yl]-2-(3-methylbutyl)-8-(2-methylpropyl)-1,3-dioxo-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxamide	215752: Compound was evaluated for its binding affinity to the trypsin enzyme	ki	0.0004	uM
(3S,3aR,6aS)-3-(4-methyl-2-oxopent-3-enyl)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	215376: Inhibition of trypsin	ic50	0.0005	uM
(2R)-1-[(2S)-3-(4-carbamimidoylphenyl)-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)sulfonylamino]propanoyl]-4-methyl-3,6-dihydro-2H-pyridine-2-carboxylic acid	215748: Binding affinity against Trypsin	ki	0.0005	uM
(3S,3aR,6aS)-3-benzyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	215376: Inhibition of trypsin	ic50	0.0006	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetic acid	254278: Inhibitory constant against trypsin	ki	0.0007	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-28,34-bis[(1R)-1-hydroxyethyl]-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-40-yl]acetamide	1251580: Inhibition of trypsin (unknown origin)	ki	0.0007	uM
4-[2-(tert-butylsulfamoyl)phenyl]-N-[(1R)-4-(diaminomethylideneamino)-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-2-methylbenzamide	215748: Binding affinity against Trypsin	ki	0.0007	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-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	1361038: Inhibition of human cationic trypsin using Boc-VPR-MCA as substrate measured every 30 secs for 10 mins	ki	0.0008	uM
(2R)-2-(benzylsulfonylamino)-5-(diaminomethylideneamino)-N-[2-[[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]amino]-2-oxoethyl]pentanamide	215722: Inhibitory activity against Trypsin	ic50	0.0008	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4-[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-19-(naphthalen-2-ylmethyl)-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	1361038: Inhibition of human cationic trypsin using Boc-VPR-MCA as substrate measured every 30 secs for 10 mins	ki	0.0009	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(6-carbamimidoyl-2-methyl-1H-indol-3-yl)acetate	1387138: Inhibition of trypsin (unknown origin) pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.0010	uM
(6S,8aS)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-oxo-2-(3-phenylpropanoyl)-1,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-6-carboxamide	215386: In vitro inhibitory activity against human trypsin	ic50	0.0010	uM
(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]pentanediamide	682988: Tight binding inhibition of human trypsin expressed in Drosophila melanogaster S2 cells using Boc-QAR-AMC as substrate incubated for 15 mins prior to substrate addition measured for 30 mins by fluorimetric analysis	ki	0.0010	uM
(6S,8aS)-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-4-oxo-2-(3-phenylpropanoyl)-1,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-6-carboxamide	215386: In vitro inhibitory activity against human trypsin	ic50	0.0010	uM
ethyl 2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetate	254278: Inhibitory constant against trypsin	ki	0.0013	uM
[4-(diaminomethylideneamino)phenyl] 4-(diaminomethylideneamino)benzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0014	uM
methyl (3S)-4-[(2R)-2-[[(1S)-3-carbamimidoyl-2-hydroxycyclohexyl]carbamoyl]pyrrolidin-1-yl]-4-oxo-3-(2-propylpentanoylamino)butanoate	215398: In vitro for inhibition of serine protease Trypsin.	ic50	0.0014	uM
tert-butyl 3-[1-[2-[[(1R)-5-amino-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]amino]-2-oxoethyl]-5-benzyl-1,2,4-triazol-3-yl]propanoate	213333: Inhibition of trypsin	ki	0.0014	uM
N-[2-(1-benzylpiperidin-2-yl)ethyl]-2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0015	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0015	uM
(4-methoxycarbonylphenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	215371: Inhibition of human trypsin and the control activity being 7.3 umol/min/mg	ic50	0.0015	uM
N-[(3S)-1-carbamimidoyl-2-hydroxypiperidin-3-yl]-2-[(3S)-3-(cyclohexylmethylsulfonylamino)-7-methoxy-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetamide;2,2,2-trifluoroacetic acid	215387: In vitro inhibitory activity against human enzyme trypsin	ic50	0.0015	uM
(2R)-N-[(1S)-3-carbamimidoyl-2-hydroxycyclohexyl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	215398: In vitro for inhibition of serine protease Trypsin.	ic50	0.0015	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]ethanol	254278: Inhibitory constant against trypsin	ki	0.0016	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264686: Inhibition of trypsin	ic50	0.0016	uM
[4-(aminomethyl)phenyl] 4-(diaminomethylideneamino)benzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0016	uM
(4-ethoxycarbonylphenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	215371: Inhibition of human trypsin and the control activity being 7.3 umol/min/mg	ic50	0.0016	uM
(4-cyanophenyl) 4-(diaminomethylideneamino)benzoate;4-methylbenzenesulfonic acid	215371: Inhibition of human trypsin and the control activity being 7.3 umol/min/mg	ic50	0.0016	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0016	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-4-[(2S)-butan-2-yl]-25,34-bis(3-carbamimidamidopropyl)-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-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	1361038: Inhibition of human cationic trypsin using Boc-VPR-MCA as substrate measured every 30 secs for 10 mins	ki	0.0019	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoylfuran-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264686: Inhibition of trypsin	ic50	0.0019	uM
N-[(1R)-5-amino-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]-2-[5-benzyl-3-(methylsulfanylmethyl)-1,2,4-triazol-1-yl]acetamide	213333: Inhibition of trypsin	ki	0.0019	uM
(3R,3aR,6aS)-3-benzyl-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one	215376: Inhibition of trypsin	ic50	0.0020	uM
(2S,4S)-1-[4-(aminomethyl)-3-methoxybenzoyl]-4-[5-(2-cyclopropylethoxy)-3,4-dihydro-1H-isoquinolin-2-yl]-N-methylpyrrolidine-2-carboxamide	1627865: Inhibition of human PRSS1 assessed as enzymatic cleavage of Benzoyl-GlyPro-Arg’Rh110-gammaGlu-OH by fluorescence analysis	ic50	0.0020	uM
ethyl (3S)-3-(benzylsulfonylamino)-1-[2-[[(2R,3S)-1-carbamimidoyl-2-hydroxypiperidin-3-yl]amino]-2-oxoethyl]-2-oxopiperidine-3-carboxylate	215390: In vitro inhibitory activity was evaluated against human trypsin cleavage of the chromogenic substrate	ic50	0.0020	uM
N-[5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-2-(2-oxo-4-quinolin-8-ylsulfonylpiperazin-1-yl)acetamide	215722: Inhibitory activity against Trypsin	ic50	0.0020	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
tetrathiomolybdate	increases expression	1
monomethylarsonous acid	increases expression	1
bisphenol B	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Diethylnitrosamine	decreases expression	1
Ivermectin	decreases expression	1
Nicotine	decreases expression	1
Potassium Dichromate	increases expression	1
Smoke	increases reaction, increases secretion	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	affects expression	1
Trichloroethylene	affects response to substance	1
Aflatoxin B1	increases methylation	1
Genistein	decreases expression	1

ChEMBL screening assays

674 unique, capped per target: 616 binding, 51 admet, 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1245068	Binding	Inhibition of human Trypsin activity	MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease. — Antimicrob Agents Chemother
CHEMBL815100	Functional	Compound was evaluated for in vitro inhibition of trypsin acting as esterase at 0.1 mM concentration	Synthesis and biological evaluation of novel coumarin derivatives with a 7-azomethine linkage. — Bioorg Med Chem Lett
CHEMBL4320630	ADMET	Stability of the compound assessed as trypsin (unknown origin)-mediated compound hydrolysis after 8 hrs by SDS-PAGE analysis	Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
NCT05245877	PHASE4	RECRUITING	Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery
NCT05784311	PHASE4	RECRUITING	Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
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