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Neutral endopeptidase

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Target not currently curated in GtoImmuPdb

Target id: 1611

Nomenclature: Neutral endopeptidase

Family: M13: Neprilysin

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 750 3q25.2 MME membrane metalloendopeptidase
Mouse 1 750 3 29.97 cM Mme membrane metallo endopeptidase
Rat 1 750 2q31 Mme membrane metallo-endopeptidase
Previous and Unofficial Names Click here for help
Enkephalinase | NEP | neprilysin | atriopeptidase | SFE | skin fibroblast elastase | CALLA | CD10 | membrane metallo-endopeptidase
Database Links Click here for help
Specialist databases
MEROPS M13.001 (Hs)
Other databases
Alphafold P08473 (Hs), Q61391 (Mm), P07861 (Rn)
BRENDA 3.4.24.11
CATH/Gene3D 3.40.390.10
ChEMBL Target CHEMBL1944 (Hs), CHEMBL2642 (Mm), CHEMBL3369 (Rn)
DrugBank Target P08473 (Hs)
Ensembl Gene ENSG00000196549 (Hs), ENSMUSG00000027820 (Mm), ENSRNOG00000009514 (Rn)
Entrez Gene 4311 (Hs), 17380 (Mm), 24590 (Rn)
Human Protein Atlas ENSG00000196549 (Hs)
KEGG Enzyme 3.4.24.11
KEGG Gene hsa:4311 (Hs), mmu:17380 (Mm), rno:24590 (Rn)
OMIM 120520 (Hs)
Pharos P08473 (Hs)
RefSeq Nucleotide NM_007289 (Hs), NM_000902 (Hs), NM_007287 (Hs), NM_007288 (Hs), NM_008604 (Mm), NM_012608 (Rn)
RefSeq Protein NP_009220 (Hs), NP_009218 (Hs), NP_009219 (Hs), NP_000893 (Hs), NP_032630 (Mm), NP_036740 (Rn)
SynPHARM 83481 (in complex with compound 1a [PMID: 25692029])
80705 (in complex with sacubitrilat)
UniProtKB P08473 (Hs), Q61391 (Mm), P07861 (Rn)
Wikipedia MME (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.24.11
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
enkephalins Substrate is endogenous in the given species Hs - -

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1b [PMID: 18078750] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pKi 3
⤷ pKi 8.9 (Ki 1.3x10-9 M) [3]
compound 1a [PMID: 25692029] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pKi 1-2
⤷ pKi 8.9 (Ki 1.4x10-9 M) [1-2]
kelatorphan Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pKi 2
⤷ pKi 8.8 (Ki 1.7x10-9 M) [2]
phosphoramidon Small molecule or natural product Ligand has a PDB structure Rn Inhibition 8.4 pKi 4
⤷ pKi 8.4 (Ki 4x10-9 M) [4]
Description: Inhibition of enkephalinase from rat kidney
fasidotrilat Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pKi 8
⤷ pKi 8.3 (Ki 5.6x10-9 M) [8]
KC-12615 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 5
⤷ pIC50 8.4 (IC50 4.2x10-9 M) [5]
sacubitrilat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 7.3x10-9 M) [7]
candoxatrilat Small molecule or natural product Hs Inhibition 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [6]
thiorphan Small molecule or natural product Ligand has a PDB structure Hs Inhibition - -
⤷
candoxatril Small molecule or natural product Hs Inhibition - -
⤷
fasidotril Small molecule or natural product Click here for species-specific activity table Hs Inhibition - -
⤷
daglutril Small molecule or natural product Click here for species-specific activity table Hs Inhibition - -
⤷
View species-specific inhibitor tables
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Membranous nephropathy, susceptibility to; MBNP
OMIM: 614692

References

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1. Bonnard E, Poras H, Nadal X, Maldonado R, Fournié-Zaluski MC, Roques BP. (2015) Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain. Pharmacol Res Perspect, 3 (2): e00116. [PMID:25692029]

2. Chen H, Noble F, Roques BP, Fournié-Zaluski MC. (2001) Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs. J Med Chem, 44 (21): 3523-30. [PMID:11585456]

3. Deaton DN, Gao EN, Graham KP, Gross JW, Miller AB, Strelow JM. (2008) Thiol-based angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1 subsite. Bioorg Med Chem Lett, 18 (2): 732-7. [PMID:18078750]

4. Elliott RL, Marks N, Berg MJ, Portoghese PS. (1985) Synthesis and biological evaluation of phosphonamidate peptide inhibitors of enkephalinase and angiotensin-converting enzyme. J Med Chem, 28 (9): 1208-16. [PMID:2993614]

5. Figueroa F, Davicino R, Micalizzi B, Oliveros L, Forneris M. (2012) Macrophage secretions modulate the steroidogenesis of polycystic ovary in rats: effect of testosterone on macrophage pro-inflammatory cytokines. Life Sci, 90 (19-20): 733-9. [PMID:22480516]

6. Leung D, Abbenante G, Fairlie DP. (2000) Protease inhibitors: current status and future prospects. J Med Chem, 43 (3): 305-41. [PMID:10669559]

7. Swedberg K. Inhibition of the renin - angiotensin system – present and future challenges. Accessed on 02/11/2014. Modified on 02/11/2014. Heart Failure Update 2014, http://www.hfupdate.ca/pdfs/Inhibition%20of%20th%20eRenin-Angiotensin%20System_Present%20and%20Future%20Challenges_Dr.%20Swedberg.pdf

8. Tsantili-Kakoulidou A, Nicolaou I, Vrakas D, Demopoulos VJ. (2005) Modelling of aldose reductase inhibitory activity of pyrrol-1-yl-acetic acid derivatives by means of multivariate statistics. Med Chem, 1 (4): 321-6. [PMID:16789889]

How to cite this page

M13: Neprilysin: Neutral endopeptidase. Last modified on 05/08/2021. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1611.