Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEVN830)

• DME Name: Neprilysin (MME)
• Synonyms: Atriopeptidase; Common acute lymphocytic leukemia antigen; Enkephalinase; Neutral endopeptidase; Neutral endopeptidase 24.11; Skin fibroblast elastase; CALLA; CD10; EPN; MME; NEP; SFE
• Gene Name: MME
• UniProt ID: NEP_HUMAN
• INTEDE ID: DME0168
• Gene ID: 4311
• EC Number:
  EC: 3.4.24.11
  Hydrolases
  Peptidase
  Metallopeptidase
  EC: 3.4.24.11
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSS
  DCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKD
  VLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGA
  SWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKE
  ACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLY
  NKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILT
  KYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNME
  NAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERI
  GYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAA
  VVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKD
  GDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYR
  AYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRII
  GTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
• Function: This enzyme has thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. It is biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond and able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. It is also involved in the degradation of atrial natriuretic factor.
• KEGG Pathway:
  Alzheimer's disease (hsa05010)
  Hematopoietic cell lineage (hsa04640)
  Protein digestion and absorption (hsa04974)
  Renin-angiotensin system (hsa04614)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DME

2 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Liraglutide	DM3FXPS	Non-insulin dependent diabetes	5A11	Approved	[40]
Semaglutide	DMAGFOD	Type-2 diabetes	5A11	Approved	[41]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	2.10E-23	-1.18E+00	-9.85E-01
Alopecia	ED70	Skin from scalp	8.10E-03	2.57E-01	3.65E-01
Alzheimer's disease	8A20	Entorhinal cortex	8.60E-02	-8.87E-02	-4.05E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	7.37E-01	-1.31E-01	-1.65E-01
Aortic stenosis	BB70	Calcified aortic valve	7.62E-01	-4.61E-02	-8.64E-02
Apnea	7A40	Hyperplastic tonsil	3.86E-01	-1.82E-01	-2.05E-01
Arthropathy	FA00-FA5Z	Peripheral blood	8.41E-02	6.97E-01	1.59E+00
Asthma	CA23	Nasal and bronchial airway	9.84E-01	-2.42E-03	-3.08E-03
Atopic dermatitis	EA80	Skin	7.31E-01	-5.72E-02	-6.72E-02
Autism	6A02	Whole blood	6.37E-01	-3.52E-02	-5.21E-02
Autoimmune uveitis	9A96	Peripheral monocyte	4.46E-02	8.34E-01	5.42E+00
Autosomal dominant monocytopenia	4B04	Whole blood	4.68E-05	-1.09E+00	-2.41E+00
Bacterial infection of gingival	1C1H	Gingival tissue	5.36E-22	1.34E+00	1.89E+00
Batten disease	5C56.1	Whole blood	3.75E-01	8.14E-02	5.44E-01
Behcet's disease	4A62	Peripheral blood	2.66E-01	1.56E-01	4.07E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	9.92E-01	-4.54E-02	-2.72E-01
Bladder cancer	2C94	Bladder tissue	5.18E-02	-7.99E-01	-1.34E+00
Breast cancer	2C60-2C6Z	Breast tissue	1.09E-229	-3.30E+00	-4.50E+00
Cardioembolic stroke	8B11.20	Whole blood	1.46E-04	5.64E-01	8.88E-01
Cervical cancer	2C77	Cervical tissue	5.41E-01	-2.57E-01	-3.80E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	7.81E-01	1.12E+00	3.65E-01
Chronic hepatitis C	1E51.1	Whole blood	4.01E-01	7.08E-02	5.22E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.60E-01	-1.36E-01	-1.94E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	4.50E-01	-2.63E-02	-4.45E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.80E-02	2.23E-01	1.32E+00
Colon cancer	2B90	Colon tissue	1.94E-43	8.66E-01	1.30E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.26E-02	2.04E-01	1.13E+00
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	3.19E-01	1.39E-01	2.96E-01
Endometriosis	GA10	Endometrium tissue	2.13E-02	-5.42E-01	-5.23E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.89E-01	9.17E-02	6.79E-01
Familial hypercholesterolemia	5C80.00	Whole blood	8.04E-19	-4.32E+00	-2.27E+00
Gastric cancer	2B72	Gastric tissue	6.05E-03	1.03E+00	4.45E+00
Glioblastopma	2A00.00	Nervous tissue	8.01E-01	8.98E-02	1.21E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	2.45E-01	-6.77E-01	-2.04E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	2.00E-01	-5.73E-02	-3.30E-02
Head and neck cancer	2D42	Head and neck tissue	6.73E-23	9.96E-01	1.84E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	4.63E-01	-4.26E-02	-5.25E-02
Huntington's disease	8A01.10	Whole blood	8.17E-01	-1.31E-02	-8.30E-02
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	8.91E-03	-1.07E+00	-2.40E+00
Immunodeficiency	4A00-4A20	Peripheral blood	6.87E-02	5.34E-02	8.35E-01
Influenza	1E30	Whole blood	9.85E-01	-9.33E-02	-6.24E-01
Interstitial cystitis	GC00.3	Bladder tissue	1.95E-01	-7.09E-01	-1.09E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.26E-02	-1.05E+00	-9.06E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	2.01E-01	-1.05E-01	-2.95E-01
Ischemic stroke	8B11	Peripheral blood	3.05E-01	9.42E-03	3.88E-02
Juvenile idiopathic arthritis	FA24	Peripheral blood	5.92E-01	1.09E-01	4.77E-02
Lateral sclerosis	8B60.4	Skin	2.75E-02	-7.88E-01	-1.40E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	1.73E-02	-4.43E-01	-8.79E-01
Liver cancer	2C12.0	Liver tissue	3.62E-07	-2.01E+00	-2.00E+00
Liver failure	DB99.7-DB99.8	Liver tissue	2.15E-05	-1.70E+00	-3.01E+00
Lung cancer	2C25	Lung tissue	9.73E-82	-2.48E+00	-2.77E+00
Lupus erythematosus	4A40	Whole blood	2.65E-04	6.22E-01	3.61E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	3.23E-01	4.00E-02	2.35E-01
Major depressive disorder	6A70-6A7Z	Whole blood	5.06E-02	2.11E-01	5.80E-01
Melanoma	2C30	Skin	7.82E-01	5.47E-02	4.42E-02
Multiple myeloma	2A83.1	Peripheral blood	2.22E-01	9.93E-02	8.47E-01
Multiple myeloma	2A83.1	Bone marrow	2.04E-03	-5.68E-01	-1.98E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	6.08E-01	1.72E-01	4.00E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.98E-28	-4.19E+00	-5.78E+00
Myelofibrosis	2A20.2	Whole blood	6.06E-02	-5.32E-01	-1.22E+00
Myocardial infarction	BA41-BA50	Peripheral blood	1.63E-05	2.45E+00	1.32E+00
Myopathy	8C70.6	Muscle tissue	5.92E-01	2.07E-02	4.91E-02
Neonatal sepsis	KA60	Whole blood	2.19E-12	-1.76E+00	-1.66E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.93E-05	-9.55E-01	-2.70E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	1.39E-02	7.30E-01	9.60E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	4.23E-01	6.46E-02	7.44E-02
Olive pollen allergy	CA08.00	Peripheral blood	7.81E-02	4.39E-01	1.21E+00
Oral cancer	2B6E	Oral tissue	6.51E-02	6.47E-01	6.26E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	2.09E-01	-5.70E-01	-4.97E-01
Osteoporosis	FB83.1	Bone marrow	2.34E-01	3.78E-01	3.44E-01
Ovarian cancer	2C73	Ovarian tissue	4.00E-06	3.79E-01	1.71E+00
Pancreatic cancer	2C10	Pancreas	6.77E-01	-4.36E-01	-4.91E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	2.20E-01	4.74E-02	3.25E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	4.12E-01	-9.21E-02	-2.62E-01
Pituitary cancer	2D12	Pituitary tissue	9.49E-02	-1.22E-01	-3.01E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.03E-01	-8.38E-02	-1.67E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	6.26E-01	-6.26E-03	-2.32E-02
Polycythemia vera	2A20.4	Whole blood	1.59E-01	8.16E-02	1.81E-01
Pompe disease	5C51.3	Biceps muscle	3.02E-04	8.44E-01	2.67E+00
Preterm birth	KA21.4Z	Myometrium	5.68E-01	-1.50E-01	-1.04E-01
Prostate cancer	2C82	Prostate	2.18E-02	-4.54E-01	-4.71E-01
Psoriasis	EA90	Skin	5.66E-01	5.44E-03	7.90E-03
Rectal cancer	2B92	Rectal colon tissue	2.18E-04	8.02E-01	2.29E+00
Renal cancer	2C90-2C91	Kidney	4.65E-03	-1.40E+00	-8.80E-01
Retinoblastoma	2D02.2	Uvea	6.39E-03	4.53E-01	4.37E+00
Rheumatoid arthritis	FA20	Synovial tissue	4.63E-02	5.83E-01	4.54E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	2.31E-01	1.13E-02	4.31E-02
Schizophrenia	6A20	Prefrontal cortex	2.97E-01	2.64E-03	1.11E-02
Schizophrenia	6A20	Superior temporal cortex	6.65E-01	-4.11E-02	-2.73E-01
Scleroderma	4A42.Z	Whole blood	8.31E-01	1.48E-01	5.14E-01
Seizure	8A60-8A6Z	Whole blood	3.33E-01	1.12E+00	8.22E-01
Sensitive skin	EK0Z	Skin	7.44E-01	-3.09E-02	-1.28E-01
Sepsis with septic shock	1G41	Whole blood	1.12E-39	-1.60E+00	-1.81E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	8.27E-02	-9.94E-01	-8.63E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.23E-02	1.19E-01	7.39E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.60E-01	-1.59E-01	-2.45E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.39E-01	5.64E-01	9.15E-01
Skin cancer	2C30-2C3Z	Skin	2.94E-08	3.48E-01	4.13E-01
Thrombocythemia	3B63	Whole blood	1.56E-01	-2.78E-01	-6.30E-01
Thrombocytopenia	3B64	Whole blood	4.63E-01	1.20E+00	1.17E+00
Thyroid cancer	2D10	Thyroid	1.74E-08	1.10E-01	1.98E-01
Tibial muscular dystrophy	8C75	Muscle tissue	1.63E-08	1.13E+00	3.22E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	7.51E-02	1.02E-01	1.10E+00
Type 2 diabetes	5A11	Liver tissue	3.54E-01	4.98E-01	9.92E-01
Ureter cancer	2C92	Urothelium	3.75E-01	-5.99E-02	-1.64E-01
Uterine cancer	2C78	Endometrium tissue	3.41E-28	-2.67E+00	-1.70E+00
Vitiligo	ED63.0	Skin	2.27E-01	-4.19E-01	-4.56E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Neutral endopeptidase (MME) DTT Info
• DME DTT Type: Clinical trial

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LCZ696	DMLFX7K	Heart failure	BD10-BD13	Approved	[1]

13 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Candoxatril	DMHJCGV	Hypertension	BA00-BA04	Phase 3	[2]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[3]
Sampatrilat	DMXTOVE	Hypotension	BA20-BA21	Phase 2	[4]
SLV 306	DMCDON3	Acute decompensated heart failure	BD1Z	Phase 2	[5]
SLV-334	DMXCJKY	Brain injury	NA07.Z	Phase 2	[6]
VX-15	DMLWM4G	Huntington disease	8A01.10	Phase 2	[7]
CART-10 cells	DMQ4UJ6	Acute lymphoblastic leukaemia	2A85	Phase 1	[8]
CD10-CART	DM0XDYT	leukaemia	2A60-2B33	Phase 1	[9]
Debio 0827	DMQIEFB	Chronic pain	MG30	Phase 1	[10]
GW-796406	DMQ46DN	Hypotension	BA20-BA21	Phase 1	[3]
Pfizer 4	DMME5P8	Female sexual arousal dysfunction	HA01.1	Phase 1	[11]
SLV-338	DM7WKTM	Cardiovascular disease	BA00-BE2Z	Phase 1	[12]
TD-0714	DMO8L6T	Heart failure	BD10-BD13	Phase 1	[13]

18 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ilepatril	DMTR50E	Diabetic nephropathy	GB61.Z	Discontinued in Phase 2/3	[14]
CGS-25462	DM2OWCV	Hypertension	BA00-BA04	Discontinued in Phase 2	[15]
Fasidotril	DMRU1KT	Hypotension	BA20-BA21	Discontinued in Phase 2	[16]
Gemopatrilat	DMLMT5O	Hypotension	BA20-BA21	Discontinued in Phase 2	[17]
M-100240	DMQ1LWU	Hypotension	BA20-BA21	Discontinued in Phase 2	[18]
SCH-32615	DMAGBM2	Pain	MG30-MG3Z	Discontinued in Phase 2	[19]
Sch-34826	DMZR6GI	Hypertension	BA00-BA04	Discontinued in Phase 2	[20]
SCH-42495	DM2RH51	Hypotension	BA20-BA21	Discontinued in Phase 2	[21]
Candoxatrilat	DMQIWZL	Heart failure	BD10-BD13	Discontinued in Phase 1	[22]
BMS-182657	DM0K4DZ	Cardiovascular disease	BA00-BE2Z	Terminated	[23]
CGS-26303	DMFZM09	N. A.	N. A.	Terminated	[24]
CGS-26393	DM4U72A	Heart disease	BA41-BA42	Terminated	[25]
CGS-30440	DM94WIO	Hypertension	BA00-BA04	Terminated	[26]
GW-660511	DMG5A1Z	Hypertension	BA00-BA04	Terminated	[27]
Omapatrilat	DMAGUY0	Hypertension	BA00-BA04	Terminated	[28]
SCH-54470	DMEWLZ7	N. A.	N. A.	Terminated	[29]
SQ-26332	DM6SW2R	N. A.	N. A.	Terminated	[30]
SQ-28603	DM9DJFS	Hypertension	BA00-BA04	Terminated	[31]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
9-Mercaptomethyl-10-oxo-azecane-2-carboxylic acid	DMM2GQC	Discovery agent	N.A.	Investigative	[32]
CGS-314447	DM514L0	Discovery agent	N.A.	Investigative	[24]
fasidotrilat	DMC8G7X	Discovery agent	N.A.	Investigative	[33]
LBQ657	DMQ2DFN	Discovery agent	N.A.	Investigative	[34]
Phosphoramidon	DM3VL7G	Discovery agent	N.A.	Investigative	[35]
PMID18078750C1b	DMO21H5	Discovery agent	N.A.	Investigative	[36]
RB-105	DMRK3HO	Hypertension	BA00-BA04	Investigative	[37]
Thiorphan	DM86LFB	Discovery agent	N.A.	Investigative	[38]
[2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala	DMI9RLZ	Discovery agent	N.A.	Investigative	[39]

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