PGA5

Summary

PGA5 (pepsinogen A5, HGNC:8887) is a protein-coding gene on chromosome 11q12.2, encoding Pepsin A-5 (P0DJD9). Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.

This gene encodes a protein precursor of the digestive enzyme pepsin, a member of the peptidase A1 family of endopeptidases. The encoded precursor is secreted by gastric chief cells and undergoes autocatalytic cleavage in acidic conditions to form the active enzyme, which functions in the digestion of dietary proteins. This gene is found in a cluster of related genes on chromosome 11, each of which encodes one of multiple pepsinogens. Pepsinogen levels in serum may serve as a biomarker for atrophic gastritis and gastric cancer.

Source: NCBI Gene 5222 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8887
Approved symbol	PGA5
Name	pepsinogen A5
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000256713
Ensembl biotype	protein_coding
OMIM	169730
Entrez	5222

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 retained_intron

ENST00000312403, ENST00000451616, ENST00000535568, ENST00000536269, ENST00000541528, ENST00000545109

RefSeq mRNA: 1 — MANE Select: NM_014224 NM_014224

CCDS: CCDS8001

Canonical transcript exons

ENST00000312403 — 9 exons

Exon	Start	End
ENSE00002460848	61245152	61245270
ENSE00002497124	61241175	61241282
ENSE00002531421	61245946	61246145
ENSE00003601922	61248419	61248535
ENSE00003631830	61244165	61244282
ENSE00003640126	61241769	61241931
ENSE00003674872	61249916	61250014
ENSE00003684985	61249669	61249813
ENSE00003899095	61251132	61251444

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 94.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	94.70	gold quality
right uterine tube	UBERON:0001302	93.30	gold quality
stomach	UBERON:0000945	92.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.99	gold quality
fundus of stomach	UBERON:0001160	86.75	gold quality
right coronary artery	UBERON:0001625	80.63	gold quality
lower esophagus mucosa	UBERON:0035834	78.01	gold quality
endocervix	UBERON:0000458	77.95	gold quality
left uterine tube	UBERON:0001303	77.84	gold quality
fallopian tube	UBERON:0003889	75.63	gold quality
ectocervix	UBERON:0012249	75.37	gold quality
body of pancreas	UBERON:0001150	72.92	gold quality
right adrenal gland	UBERON:0001233	72.68	gold quality
right lobe of liver	UBERON:0001114	72.65	gold quality
mucosa of transverse colon	UBERON:0004991	72.52	gold quality
uterine cervix	UBERON:0000002	72.08	gold quality
spleen	UBERON:0002106	72.07	gold quality
right ovary	UBERON:0002118	71.83	gold quality
left adrenal gland	UBERON:0001234	71.68	gold quality
left ovary	UBERON:0002119	70.38	gold quality
omental fat pad	UBERON:0010414	70.09	gold quality
transverse colon	UBERON:0001157	70.04	gold quality
metanephros cortex	UBERON:0010533	70.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.85	gold quality
adipose tissue	UBERON:0001013	69.84	gold quality
right lung	UBERON:0002167	69.15	gold quality
body of uterus	UBERON:0009853	68.31	gold quality
ovary	UBERON:0000992	68.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.14	gold quality
left lobe of thyroid gland	UBERON:0001120	67.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX2

miRNA regulators (miRDB)

5 targeting PGA5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-194-3P	97.36	65.96	1027

Literature-anchored findings (GeneRIF, showing 4)

• Levels of pepsinogen/pepsin A and C are higher in the mouth swabs of preterm infants with gastroesophageal reflux. (PMID:23311720)
• Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME. (PMID:24284944)
• Local synthesis of pepsin and proton pumps in BE and EAC is not uncommon. Absence of these molecules in normal (noncancer) esophagi, SCC, and in vitro data support a role for pepsin in reflux-attributed carcinogenic changes in the esophagus (PMID:31046139)
• The Role of Salivary Pepsin in the Diagnosis of Gastroesophageal Reflux Disease (GERD) Evaluated Using High-Resolution Manometry and 24-Hour Multichannel Intraluminal Impedance-pH Monitoring. (PMID:33220027)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Bace	FBGN0032049
drosophila_melanogaster	CG6508	FBGN0032303
drosophila_melanogaster	CG17134	FBGN0032304
drosophila_melanogaster	CG33128	FBGN0053128
caenorhabditis_elegans		WBGENE00000214
caenorhabditis_elegans		WBGENE00000218
caenorhabditis_elegans		WBGENE00012681
caenorhabditis_elegans		WBGENE00012682
caenorhabditis_elegans		WBGENE00012683
caenorhabditis_elegans		WBGENE00013973
caenorhabditis_elegans		WBGENE00017678
caenorhabditis_elegans		WBGENE00019104
caenorhabditis_elegans		WBGENE00019105
caenorhabditis_elegans		WBGENE00077655

Paralogs (9): PGC (ENSG00000096088), CTSD (ENSG00000117984), NAPSA (ENSG00000131400), REN (ENSG00000143839), BACE2 (ENSG00000182240), BACE1 (ENSG00000186318), CTSE (ENSG00000196188), PGA4 (ENSG00000229183), PGA3 (ENSG00000229859)

Protein

Protein identifiers

Pepsin A-5 — P0DJD9 (reviewed: P0DJD9)

Alternative names: Pepsinogen-5

All UniProt accessions (3): C9JM59, P0DJD9, F5GWT0

UniProt curated annotations — full annotation on UniProt →

Function. Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.

Subcellular location. Secreted.

Similarity. Belongs to the peptidase A1 family.

RefSeq proteins (1): NP_055039* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001461	Aspartic_peptidase_A1	Family
IPR001969	Aspartic_peptidase_AS	Active_site
IPR012848	Aspartic_peptidase_N	Domain
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033121	PEPTIDASE_A1	Domain
IPR034162	Pepsin_A	Domain

Pfam: PF00026, PF07966

UniProt features (18 total): sequence conflict 8, disulfide bond 3, active site 2, signal peptide 1, propeptide 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DJD9-F1	91.28	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 94; 277

Post-translational modifications (1): 130

Disulfide bonds (3): 107–112, 268–272, 311–344

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism

MSigDB gene sets: 32 (showing top): GOBP_DIGESTION, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, YAMAZAKI_TCEB3_TARGETS_UP, VECCHI_GASTRIC_CANCER_EARLY_DN, GOCC_MULTIVESICULAR_BODY, GOCC_ENDOSOME_LUMEN, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_ASPARTIC_TYPE_PEPTIDASE_ACTIVITY, FOSTER_KDM1A_TARGETS_UP, GOCC_LATE_ENDOSOME_LUMEN, GOCC_MULTIVESICULAR_BODY_LUMEN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_SURFACTANT_METABOLISM

GO Biological Process (2): proteolysis (GO:0006508), digestion (GO:0007586)

GO Molecular Function (3): aspartic-type endopeptidase activity (GO:0004190), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular exosome (GO:0070062), multivesicular body lumen (GO:0097486), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
multicellular organismal process	1
endopeptidase activity	1
aspartic-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
extracellular vesicle	1
multivesicular body	1
late endosome lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

BioGRID (1): PGA5 (Synthetic Lethality)

ESM2 similar proteins: O93428, P00791, P00792, P00793, P00794, P00795, P03954, P03955, P04073, P0DJD7, P0DJD8, P0DJD9, P11489, P14091, P16228, P16476, P18276, P20142, P25796, P27677, P27678, P27821, P27822, P27823, P28712, P28713, P43159, P56272, P70269, P81497, P81498, Q03168, Q28389, Q64411, Q689Z7, Q800A0, Q805F2, Q805F3, Q8SQ41, Q9D7R7

Diamond homologs: A0A146F0J0, A1CBR4, A1DDK1, A2R3L3, B0Y1V8, B6HL60, B8MF81, B8NLY9, C5FBS2, C5FW52, C5FZ57, C5PEI9, D4AIC4, D4ANC3, D4AT39, D4D7C5, D4DE18, D4DGR1, E5A7T3, E5R1B9, O01530, O13340, O60020, O65390, O76856, O93885, P00791, P00792, P00798, P03954, P03955, P04073, P06026, P0CU33, P0DJD7, P0DJD8, P0DJD9, P10602, P11489, P11838

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

889 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61241283:G:GG	donor_gain	1.0000
11:61241765:ACAG:A	acceptor_gain	1.0000
11:61241767:A:AG	acceptor_gain	1.0000
11:61241767:A:AT	acceptor_loss	1.0000
11:61241767:AG:A	acceptor_gain	1.0000
11:61241767:AGG:A	acceptor_gain	1.0000
11:61241768:G:GA	acceptor_gain	1.0000
11:61241768:GG:G	acceptor_gain	1.0000
11:61241768:GGG:G	acceptor_gain	1.0000
11:61241768:GGGT:G	acceptor_gain	1.0000
11:61241768:GGGTC:G	acceptor_gain	1.0000
11:61241865:A:T	donor_gain	1.0000
11:61241927:TGGAT:T	donor_gain	1.0000
11:61241928:GGAT:G	donor_gain	1.0000
11:61241928:GGATG:G	donor_gain	1.0000
11:61241929:G:GT	donor_gain	1.0000
11:61241929:GAT:G	donor_gain	1.0000
11:61241930:AT:A	donor_gain	1.0000
11:61241931:TG:T	donor_loss	1.0000
11:61241932:G:GG	donor_gain	1.0000
11:61241933:T:A	donor_loss	1.0000
11:61245147:T:TA	acceptor_gain	1.0000
11:61245148:GCAG:G	acceptor_loss	1.0000
11:61245149:CA:C	acceptor_loss	1.0000
11:61245150:A:AG	acceptor_gain	1.0000
11:61245150:AG:A	acceptor_loss	1.0000
11:61245151:G:GT	acceptor_gain	1.0000
11:61245151:GC:G	acceptor_gain	1.0000
11:61245151:GCC:G	acceptor_gain	1.0000
11:61245151:GCCA:G	acceptor_gain	1.0000

AlphaMissense

2544 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61249724:G:C	D277H	0.999
11:61249725:A:C	D277A	0.999
11:61249725:A:T	D277V	0.999
11:61249726:C:A	D277E	0.999
11:61249726:C:G	D277E	0.999
11:61251195:T:A	W361R	0.999
11:61251195:T:C	W361R	0.999
11:61244226:A:C	D94A	0.998
11:61244226:A:T	D94V	0.998
11:61244227:C:A	D94E	0.998
11:61244227:C:G	D94E	0.998
11:61244229:C:T	T95I	0.998
11:61246039:G:T	G184W	0.998
11:61248516:T:A	W252R	0.998
11:61248516:T:C	W252R	0.998
11:61249725:A:G	D277G	0.998
11:61251205:G:T	G364V	0.998
11:61244226:A:G	D94G	0.997
11:61244246:T:A	W101R	0.997
11:61244246:T:C	W101R	0.997
11:61244265:G:A	C107Y	0.997
11:61244266:C:G	C107W	0.997
11:61246039:G:A	G184R	0.997
11:61246039:G:C	G184R	0.997
11:61246040:G:A	G184E	0.997
11:61248518:G:C	W252C	0.997
11:61248518:G:T	W252C	0.997
11:61249724:G:T	D277Y	0.997
11:61249731:G:A	G279D	0.997
11:61249731:G:T	G279V	0.997

dbSNP variants (sampled 300 via entrez): RS1000278023 (11:61247559 G>A), RS1000705657 (11:61250582 G>A), RS1000944254 (11:61250792 G>A,C,T), RS1001177376 (11:61251004 A>C), RS1001195355 (11:61249475 A>C,G), RS1001335459 (11:61247233 T>C), RS1001428498 (11:61247039 T>C), RS1002342948 (11:61240475 C>T), RS1002585592 (11:61250159 A>G), RS1003186058 (11:61249294 C>T), RS1003633242 (11:61247493 G>T), RS1004168785 (11:61250396 G>C,T), RS1004219218 (11:61250228 G>A), RS1004567455 (11:61249086 G>A), RS1004697369 (11:61248969 C>G)

Disease associations

OMIM: gene MIM:169730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3295 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,607 (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
CHEMBL222559	TIPRANAVIR	4	17,513
CHEMBL296588	PEPSTATIN	2	26,094

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — A1: Pepsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 8410973]	Inhibition	7.96	pKi

ChEMBL bioactivities

28 potent at pChembl≥5 of 31 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL3143435
8.82	Ki	1.5	nM	CHEMBL3143437
8.38	IC50	4.2	nM	CHEMBL154795
8.22	IC50	6	nM	CHEMBL154795
7.96	Ki	11	nM	CHEMBL287423
7.89	Ki	13	nM	CHEMBL62380
7.80	Ki	16	nM	CHEMBL87025
7.62	Ki	24	nM	CHEMBL88415
7.57	Ki	27	nM	CHEMBL313773
7.24	Ki	57	nM	CHEMBL84970
7.23	IC50	59	nM	PEPSTATIN
7.16	Ki	69	nM	CHEMBL88356
7.11	Ki	77	nM	CHEMBL316095
6.73	Ki	185	nM	CHEMBL329220
6.29	Ki	516	nM	CHEMBL88526
6.16	IC50	700	nM	CHEMBL3142364
6.10	IC50	790	nM	CHEMBL3142349
6.08	IC50	830	nM	CHEMBL63831
6.04	IC50	910	nM	CHEMBL3142354
5.97	IC50	1070	nM	CHEMBL3142353
5.92	Ki	1200	nM	CHEMBL3143436
5.91	Ki	1240	nM	CHEMBL88340
5.91	IC50	1240	nM	CHEMBL3142367
5.70	Ki	2000	nM	TIPRANAVIR
5.52	Ki	3000	nM	CHEMBL432424
5.40	IC50	4000	nM	CHEMBL326831
5.39	IC50	4100	nM	CHEMBL178421
5.27	IC50	5400	nM	CHEMBL359756

PubChem BioAssay actives

28 with measured affinity, of 60 total; 27 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-methylbutyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-3-hydroxy-6-methyl-1-[[(2S)-1-(3-methylbutylamino)-1-oxopropan-2-yl]amino]-1-oxoheptan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156896: Inhibition of pepsin	ki	0.0001	uM
3-methylbutyl N-[(2S)-1-[[(2S)-1-[[(3R,4S)-3-hydroxy-3,6-dimethyl-1-[[(2S)-1-(3-methylbutylamino)-1-oxopropan-2-yl]amino]-1-oxoheptan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156896: Inhibition of pepsin	ki	0.0015	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[2,2-difluoro-6-methyl-1-[[(2S,3S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]amino]-1,3-dioxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	156592: Inhibition of human pepsin at pH 2.0	ic50	0.0042	uM
(4S)-5-cyclohexyl-2,2-difluoro-N-(2-morpholin-4-ylethyl)-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]-3-oxopentanamide	156591: Binding affinity against human pepsin	ki	0.0110	uM
(2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	156591: Binding affinity against human pepsin	ki	0.0130	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-5-(1,3-dithian-2-yl)-3,5-dihydroxypentan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	156591: Binding affinity against human pepsin	ki	0.0160	uM
(4S)-5-cyclohexyl-2,2-difluoro-N-[(2S)-2-methylbutyl]-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]-3-oxopentanamide	156591: Binding affinity against human pepsin	ki	0.0240	uM
(3R,4S)-5-cyclohexyl-2,2-difluoro-3-hydroxy-N-[(2S)-2-methylbutyl]-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]pentanamide	156591: Binding affinity against human pepsin	ki	0.0270	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxy-6-methylheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	156591: Binding affinity against human pepsin	ki	0.0570	uM
(3S,4S)-3-hydroxy-4-[[(2S)-2-[[(3S,4S)-3-hydroxy-6-methyl-4-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-methylbutanoylamino)butanoyl]amino]butanoyl]amino]heptanoyl]amino]propanoyl]amino]-6-methylheptanoic acid	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	0.0590	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	156591: Binding affinity against human pepsin	ki	0.0690	uM
(2S)-N-[(2S,3S,5R)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	156591: Binding affinity against human pepsin	ki	0.0770	uM
methyl (3S)-4-[[(2S,3S,5R)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]amino]-3-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]-4-oxobutanoate	156591: Binding affinity against human pepsin	ki	0.1850	uM
(2S)-N-[2-[[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]amino]-2-oxo-1-prop-2-enylsulfanylethyl]-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanamide	156591: Binding affinity against human pepsin	ki	0.5160	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxyundecan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	0.7000	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxy-2-methyltridecan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	0.7900	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxy-2-methylundecan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	0.8300	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxynonan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	0.9100	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxytridecan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	1.0700	uM
3-methylbutyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-3-hydroxy-3,6-dimethyl-1-[[(2S)-1-(3-methylbutylamino)-1-oxopropan-2-yl]amino]-1-oxoheptan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156896: Inhibition of pepsin	ki	1.2000	uM
(3R,4S)-5-cyclohexyl-2,2-difluoro-3-hydroxy-N-(2-morpholin-4-ylethyl)-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]pentanamide	156591: Binding affinity against human pepsin	ki	1.2400	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(4S)-5-hydroxy-2-methylnonan-4-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	156895: Inhibitory activity against pepsin as oxidation of o-phenylenediamine by Horse radish peroxidase (Pepsin sensitive)	ic50	1.2400	uM
Tipranavir	156598: Inhibition of human pepsin	ki	2.0000	uM
(3R)-3-hydroxy-6-methyl-N-[(2S)-1-(3-methylbutylamino)-1-oxopropan-2-yl]-4-[[(2R)-3-methyl-2-(3-methylbutanoylamino)butanoyl]amino]heptanamide	156897: Pepsin inhibition using synthetic heptapeptide substrate Phe-Gly-His-Phe-(N02)-Phe-Ala- Phe-OMe	ki	3.0000	uM
3-[8,13-bis[1,2-bis(cyclopropene-1-carbonyloxy)ethyl]-18-(2-carboxyethyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid	156900: Inhibitory concentration against pepsin	ic50	4.0000	uM
(2S)-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid	240815: Inhibitory concentration against pepsin	ic50	4.1000	uM
(2S)-6-(9H-fluoren-9-ylmethoxycarbonylamino)-2-[(4-methylphenyl)sulfonyl-(2-methylpropyl)amino]hexanoic acid	240815: Inhibitory concentration against pepsin	ic50	5.4000	uM

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
azoxystrobin	increases expression	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrimidifen	increases expression	1
thifluzamide	increases expression	1
pyrachlostrobin	increases expression	1
picoxystrobin	increases expression	1
Antimycin A	increases expression	1
Benzo(a)pyrene	increases methylation	1
Rotenone	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

23 unique, capped per target: 21 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3365828	Binding	Inhibition of human recombinant pepsinogen A expressed in Escherichia coli using fluorescence-quenched Dabcyl-E-R-Nle-F-L-S-F-P-EDANS substrate by fluorimetric assay	Structure-based design of substituted piperidines as a new class of highly efficacious oral direct Renin inhibitors. — ACS Med Chem Lett
CHEMBL757034	Functional	Inhibitory activity against human pepsin at 1*10e-5 M	Design of a well-absorbed renin inhibitor. — J Med Chem

Clinical trials (associated diseases)

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