MEP1A

Summary

MEP1A (meprin A subunit alpha, HGNC:7015) is a protein-coding gene on chromosome 6p12.3, encoding Meprin A subunit alpha (Q16819).

Enables metallodipeptidase activity. Involved in epidermal growth factor receptor ligand maturation. Located in extracellular exosome. Part of meprin A complex. Is active in plasma membrane.

Source: NCBI Gene 4224 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 124 total
• Druggable target: yes
• MANE Select transcript: NM_005588

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7015
Approved symbol	MEP1A
Name	meprin A subunit alpha
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PPHA
Ensembl gene	ENSG00000112818
Ensembl biotype	protein_coding
OMIM	600388
Entrez	4224

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000230588, ENST00000611727, ENST00000680229, ENST00000680769, ENST00000879644, ENST00000879645, ENST00000879646, ENST00000879647, ENST00000879648

RefSeq mRNA: 1 — MANE Select: NM_005588 NM_005588

CCDS: CCDS4918

Canonical transcript exons

ENST00000230588 — 14 exons

Exon	Start	End
ENSE00000754998	46809420	46809537
ENSE00000755050	46819529	46819704
ENSE00000755153	46825272	46825493
ENSE00000755199	46826354	46826503
ENSE00000755313	46829356	46829571
ENSE00000755348	46833074	46833538
ENSE00000755463	46834578	46834751
ENSE00000850395	46793389	46793467
ENSE00000850396	46793552	46793576
ENSE00000850397	46793666	46793716
ENSE00000850398	46799106	46799181
ENSE00000850399	46838980	46839778
ENSE00001010022	46798606	46798646
ENSE00001710916	46835249	46835549

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 99.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.1019 / max 1786.7470, expressed in 111 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68153	3.1019	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.81	gold quality
ileum	UBERON:0002116	99.80	gold quality
jejunal mucosa	UBERON:0000399	99.70	gold quality
colonic mucosa	UBERON:0000317	98.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.80	gold quality
rectum	UBERON:0001052	97.52	gold quality
mucosa of transverse colon	UBERON:0004991	95.92	gold quality
duodenum	UBERON:0002114	95.71	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.76	gold quality
small intestine	UBERON:0002108	89.77	gold quality
transverse colon	UBERON:0001157	84.37	gold quality
sperm	CL:0000019	82.82	silver quality
male germ cell	CL:0000015	80.07	silver quality
intestine	UBERON:0000160	78.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.02	silver quality
jejunum	UBERON:0002115	75.16	gold quality
vermiform appendix	UBERON:0001154	74.56	gold quality
large intestine	UBERON:0000059	74.05	gold quality
colon	UBERON:0001155	73.00	gold quality
caecum	UBERON:0001153	70.28	gold quality
amniotic fluid	UBERON:0000173	66.48	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.54	gold quality
buccal mucosa cell	CL:0002336	60.34	gold quality
colonic epithelium	UBERON:0000397	57.44	gold quality
pancreatic ductal cell	CL:0002079	56.50	silver quality
smooth muscle tissue	UBERON:0001135	56.09	gold quality
sigmoid colon	UBERON:0001159	56.04	gold quality
endometrium epithelium	UBERON:0004811	54.92	gold quality
body of pancreas	UBERON:0001150	54.28	gold quality
lymph node	UBERON:0000029	52.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	68.59
E-ANND-3	yes	6.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, HNF1B

miRNA regulators (miRDB)

46 targeting MEP1A, 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-5696	99.98	72.36	4487
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-4478	99.07	65.16	2320

Literature-anchored findings (GeneRIF, showing 14)

• activation in colorectal cancer triggered by the plasminogen-activating system (PMID:12189145)
• The combination of these polymorphisms could not be found in any control individuals, suggesting that they might be involved in genetic predisposition to migraine in this family. (PMID:16378686)
• Mephrin beta induced a dramatic change in cell morphology and reduced the cell number, indicating a function in terminal differentiation, whereas meprin alpha did not affect cell viability, and may play a role in basal keratinocyte proliferation. (PMID:17195012)
• MEP1A is a UC susceptibility gene and indicate that decreased meprin-alpha expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD. (PMID:19262505)
• meprins could be important players in several remodeling processes involving collagen fiber deposition (PMID:20631730)
• Cystatin C was an inhibitor for human meprin alpha(K(i) = 8.5 x 10(-6) M) but, interestingly, not for meprin beta. (PMID:20806899)
• Meprin-alpha activity is regulated differently in primary tumors and metastases of colorectal cancer. By virtue of its pro-migratory and pro-angiogenic activity, meprin-alpha may promote tumor progression in colorectal cancer. (PMID:22096485)
• The present results indicate that a TNF-alpha-mediated down-regulation of CDX2 can be related to suppressed expression of MEP1A during intestinal inflammation. (PMID:22326557)
• Proteolytically active meprinalpha leads to an increase in EGFR and ERK1/2 phosphorylation and subsequently enhances cell proliferation and migration (PMID:22923609)
• Variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism in overweight/obese central European women with polycystic ovary syndrome. (PMID:24388959)
• Meprin metalloproteases A and B inactivate interleukin 6 (PMID:24474695)
• Results showed that MEP1A expression was elevated in colorectal cancer (CRC) tissues at both the mRNA and protein levels, and provided evidence for its functionally crucial role in CRC carcinogenesis as tumor proliferation and invasion. (PMID:27378469)
• Mep1A is overexpressed in most hepatocellular carcinomas and induces tumor cell migration and invasion. Mep1A expression is regulated by Reptin, and Mep1A mediates Reptin-induced migration. (PMID:27999200)
• In this review we report on recent findings that summarize the complex molecular regulation of meprins, particular folding, activation and shedding. Dysregulation of meprin alpha and meprin beta is often associated with pathological conditions such as neurodegeneration, inflammatory bowel disease and fibrosis (PMID:28502593)

Cross-species orthologs

0 orthologs

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Meprin A subunit alpha — Q16819 (reviewed: Q16819)

Alternative names: Endopeptidase-2, N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit alpha, PABA peptide hydrolase, PPH alpha

All UniProt accessions (3): Q16819, A0A7P0Z478, B7ZL91

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homotetramer consisting of disulfide-linked alpha subunits, homooligomer consisting of disulfide-linked alpha subunit homodimers, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity.

Subcellular location. Membrane.

Post-translational modifications. N-glycosylated; contains GlcNAc, galactose, mannose and a small amount of fucose.

Activity regulation. Inhibited by several hydroxamate compounds, the most potent inhibitor is actinonin.

Cofactor. Binds 1 zinc ion per subunit.

RefSeq proteins (1): NP_005579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR000998	MAM_dom	Domain
IPR001506	Peptidase_M12A	Domain
IPR002083	MATH/TRAF_dom	Domain
IPR006026	Peptidase_Metallo	Domain
IPR008294	Meprin	Family
IPR008974	TRAF-like	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034038	ZnMP_meprin	Domain

Pfam: PF00008, PF00629, PF01400, PF22486

Enzyme classification (BRENDA):

• EC 3.4.24.18 — meprin A (BRENDA: 6 organisms, 243 substrates, 90 inhibitors, 44 Km, 40 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BRADYKININ	0.0121–0.224	5
CHOLECYSTOKININ 8-SULFATE	0.11–0.49	4
SUBSTANCE P	0.0306–0.118	3
ALPHA-MSH	0.0223–0.292	2
KKGYVADAP-4-NITROANILIDE	0.024	2
LUTEINIZING HORMONE RELEASING HORMONE LHRH	0.0565–0.156	2
PROTEIN PTH12-34	0.018–0.0672	2
SECRETIN	0.0339–0.111	2
2-AMINOBENZOYL-ARG-GLY-PRO-PHE-SER-PRO-(4-NITRO)	0.22	1
2-AMINOBENZOYL-ARG-HYP-GLY-PHE-SER-PRO-(4-NITRO)	0.183	1
2-AMINOBENZOYL-ARG-PRO-GLY-ALA-SER-PRO-(4-NITRO)	1.38	1
2-AMINOBENZOYL-ARG-PRO-GLY-GLU-SER-PRO-(4-NITRO)	1.22	1
2-AMINOBENZOYL-ARG-PRO-GLY-LEU-SER-PRO-(4-NITRO)	2.46	1
2-AMINOBENZOYL-ARG-PRO-GLY-LYS-SER-PRO-(4-NITRO)	0.402	1
2-AMINOBENZOYL-ARG-PRO-ILE-PHE-SER-PRO-(4-NITRO)	0.296	1

UniProt features (103 total): strand 34, helix 18, glycosylation site 8, disulfide bond 8, sequence conflict 8, turn 7, sequence variant 5, domain 4, binding site 3, topological domain 2, signal peptide 1, propeptide 1, region of interest 1, active site 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7UAF	ELECTRON MICROSCOPY	2.4
7UAE	ELECTRON MICROSCOPY	2.6
7UAC	ELECTRON MICROSCOPY	2.7
7UAI	ELECTRON MICROSCOPY	2.8
7UAB	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16819-F1	84.92	0.68

Functional residue map

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

Catalytic / active sites (1): 156

Ligand- & substrate-binding residues (3): 155; 159; 165

Disulfide bonds (8): 107–259, 128–147, 269–431, 277, 308, 674–685, 679–694, 696–709

Glycosylation sites (8): 140, 222, 258, 414, 440, 447, 539, 630

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_64, GOBP_REGULATION_OF_HORMONE_LEVELS, CERVERA_SDHB_TARGETS_1_DN, GOBP_PROTEIN_MATURATION, chr6p12, GOBP_AMIDE_METABOLIC_PROCESS, MODULE_99, LIAO_METASTASIS, AACTTT_UNKNOWN, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOBP_PROTEOLYSIS, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_DIPEPTIDASE_ACTIVITY

GO Biological Process (3): epidermal growth factor receptor ligand maturation (GO:0038004), signaling receptor ligand precursor processing (GO:0140448), proteolysis (GO:0006508)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), metallodipeptidase activity (GO:0070573), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), meprin A complex (GO:0017090), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane protein ectodomain proteolysis	1
peptide hormone processing	1
protein processing	1
protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
metalloexopeptidase activity	1
dipeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
membrane protein complex	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEP1A	GSTA2	P09210	619
MEP1A	NTS	P30990	605
MEP1A	C1R	P00736	599
MEP1A	KLK11	Q9UBX7	561
MEP1A	ACE2	Q9BYF1	556
MEP1A	MSR1	P21757	523
MEP1A	PRCP	P42785	521
MEP1A	MGAM2	Q2M2H8	511
MEP1A	TMEM174	Q8WUU8	503
MEP1A	KNG1	P01042	501
MEP1A	SI	P14410	486
MEP1A	MGAM	O43451	477
MEP1A	TGFA	P01135	453
MEP1A	XPNPEP2	O43895	438
MEP1A	TTR	P02766	433

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MEP1A	MMP9	psi-mi:“MI:0194”(cleavage reaction)	0.560
MMP9	MEP1A	psi-mi:“MI:0194”(cleavage reaction)	0.560

BioGRID (13): KNG1 (Biochemical Activity), MEP1A (Synthetic Lethality), NPY (Biochemical Activity), NTS (Biochemical Activity), GNRH1 (Biochemical Activity), PTH (Biochemical Activity), VIP (Biochemical Activity), LAMA5 (Biochemical Activity), LAMA1 (Biochemical Activity), MEP1A (Co-purification), FN1 (Biochemical Activity), MEP1A (Synthetic Lethality), MEP1A (Affinity Capture-MS)

ESM2 similar proteins: A0A0N9E2K8, A0A1D5NSK0, A0A8M9PFP2, G5ECS8, G5EFD9, O15072, O18767, O43909, O60882, O62806, O77656, O93470, P07152, P22003, P23097, P28825, P29788, P33435, P49003, P57748, P79287, Q10835, Q11005, Q14703, Q16819, Q16820, Q19791, Q24025, Q3U435, Q568B8, Q61847, Q64230, Q6GQB9, Q6NP60, Q8CGD2, Q8K3F2, Q8N119, Q8R4K8, Q8VDA1, Q90YC2

Diamond homologs: A0A0C5PRQ1, A0FKN6, A8Q2D1, C9D7R2, C9D7R3, D2KBH9, D5FM34, D5FM37, D5FM38, K7Z9Q9, O16977, O17264, O43897, O57382, O57460, O62243, P07584, P0DM61, P0DM62, P13497, P28825, P28826, P31579, P31580, P31581, P42674, P55112, P55113, P55114, P55115, P84748, P91137, P98060, P98061, P98063, P98068, P98069, P98070, Q16819, Q16820

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDX2	“up-regulates quantity by expression”	MEP1A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2738 predictions. Top by Δscore:

Variant	Effect	Δscore
6:46793715:AGGTG:A	donor_loss	1.0000
6:46793717:G:GG	donor_gain	1.0000
6:46793717:GT:G	donor_loss	1.0000
6:46793718:T:A	donor_loss	1.0000
6:46809502:A:T	donor_gain	1.0000
6:46819655:G:GT	donor_gain	1.0000
6:46829444:G:GT	donor_gain	1.0000
6:46829482:G:GT	donor_gain	1.0000
6:46829482:G:T	donor_gain	1.0000
6:46832834:T:G	donor_gain	1.0000
6:46833319:GGA:G	donor_gain	1.0000
6:46834486:T:A	acceptor_gain	1.0000
6:46793664:A:AG	acceptor_gain	0.9900
6:46793665:G:GG	acceptor_gain	0.9900
6:46793665:GT:G	acceptor_gain	0.9900
6:46793665:GTA:G	acceptor_gain	0.9900
6:46793665:GTAC:G	acceptor_gain	0.9900
6:46793712:TTTAG:T	donor_gain	0.9900
6:46793713:TTAG:T	donor_gain	0.9900
6:46795100:GC:G	donor_gain	0.9900
6:46798586:A:AG	acceptor_gain	0.9900
6:46798587:A:G	acceptor_gain	0.9900
6:46809418:A:AG	acceptor_gain	0.9900
6:46809419:G:GG	acceptor_gain	0.9900
6:46821917:G:GT	donor_gain	0.9900
6:46821933:GG:G	donor_gain	0.9900
6:46821934:GG:G	donor_gain	0.9900
6:46825489:TTGCA:T	donor_gain	0.9900
6:46825490:TGCA:T	donor_gain	0.9900
6:46825491:GCA:G	donor_gain	0.9900

AlphaMissense

4988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:46799144:G:C	W75C	0.996
6:46799144:G:T	W75C	0.996
6:46819663:G:C	R172P	0.995
6:46826442:G:C	W289C	0.994
6:46826442:G:T	W289C	0.994
6:46833426:G:C	W499C	0.994
6:46833426:G:T	W499C	0.994
6:46835500:T:A	C679S	0.994
6:46835501:G:C	C679S	0.994
6:46835518:T:A	C685S	0.994
6:46835519:G:C	C685S	0.994
6:46799142:T:A	W75R	0.992
6:46799142:T:C	W75R	0.992
6:46819530:T:A	C128S	0.992
6:46819531:G:C	C128S	0.992
6:46819654:G:C	R169T	0.992
6:46819655:G:C	R169S	0.992
6:46819655:G:T	R169S	0.992
6:46825286:T:C	F191L	0.992
6:46825288:T:A	F191L	0.992
6:46825288:T:G	F191L	0.992
6:46833424:T:A	W499R	0.991
6:46833424:T:C	W499R	0.991
6:46809486:T:C	F110S	0.990
6:46819654:G:T	R169M	0.990
6:46825287:T:G	F191C	0.990
6:46833143:T:C	F405S	0.990
6:46833295:A:C	S456R	0.990
6:46833297:C:A	S456R	0.990
6:46833297:C:G	S456R	0.990

dbSNP variants (sampled 300 via entrez): RS1000014173 (6:46841175 A>G), RS1000023118 (6:46799033 G>A,C), RS1000074943 (6:46811385 T>C), RS1000092142 (6:46792494 T>G), RS1000135648 (6:46816743 A>G), RS1000142743 (6:46802690 C>T), RS1000149528 (6:46841672 C>G,T), RS1000207821 (6:46792768 C>A), RS1000283603 (6:46814329 G>A,C,T), RS1000290677 (6:46819983 C>A), RS1000554805 (6:46791746 T>A), RS1000731243 (6:46826030 T>C), RS1000804423 (6:46803992 A>C), RS1000871733 (6:46845473 C>T), RS1000918967 (6:46797214 T>C)

Disease associations

OMIM: gene MIM:600388 | 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): CHEMBL4105775 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 10 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.43	IC50	368	nM	CHEMBL4205925
6.20	IC50	626	nM	CHEMBL4209993
6.08	IC50	830	nM	CHEMBL4217178
5.83	IC50	1470	nM	CHEMBL4203115
5.75	IC50	1795	nM	CHEMBL4206683
5.48	IC50	3290	nM	CHEMBL4078433
5.48	IC50	3293	nM	CHEMBL4078433
5.47	IC50	3420	nM	CHEMBL4217240

PubChem BioAssay actives

8 with measured affinity, of 11 total; 7 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
2-[bis[(4-chloro-2-fluoro-3-hydroxyphenyl)methyl]amino]-N-hydroxyacetamide	1375445: Inhibition of recombinant human meprin alpha expressed in insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	ic50	0.3680	uM
2-[bis[(2,4-difluoro-3-hydroxyphenyl)methyl]amino]-N-hydroxyacetamide	1375445: Inhibition of recombinant human meprin alpha expressed in insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	ic50	0.6260	uM
2-[bis(1,3-benzodioxol-5-ylmethyl)amino]-N-hydroxyacetamide	1375473: Inhibition of meprin alpha (unknown origin)	ic50	0.8300	uM
2-[bis[(3-cyanophenyl)methyl]amino]-N-hydroxyacetamide	1375473: Inhibition of meprin alpha (unknown origin)	ic50	1.4700	uM
3-[[(4-chlorophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid	1375445: Inhibition of recombinant human meprin alpha expressed in insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	ic50	1.7950	uM
3-[[[2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid	1450129: Inhibition of recombinant human meprin alpha expressed in S2 insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	ic50	3.2900	uM
3-[[[2-(hydroxyamino)-2-oxoethyl]-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid	1375445: Inhibition of recombinant human meprin alpha expressed in insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	ic50	3.4200	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	decreases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Quercetin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4018051	ADMET	Inhibition of recombinant human meprin alpha expressed in S2 insect cells using Abz-YVADAPK(Dnp)G-OH as substrate by fluorescence assay	First insight into structure-activity relationships of selective meprin β inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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