Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFRITPU)

• DOT Name: Neurolysin, mitochondrial (NLN)
• Synonyms: EC 3.4.24.16; Angiotensin-binding protein; Microsomal endopeptidase; MEP; Mitochondrial oligopeptidase M; Neurotensin endopeptidase
• Gene Name: NLN
• Related Disease:
  Charcot-Marie-Tooth disease type 2
  Chromosomal disorder
  Cone-rod dystrophy 2
  Advanced cancer
  Alzheimer disease
  Cardiac failure
  Cerebral infarction
  Cocaine addiction
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Cystic fibrosis
  Duchenne muscular dystrophy
  Fanconi anemia complementation group A
  Fanconi's anemia
  Hepatocellular carcinoma
  Matthew-Wood syndrome
  Neuralgia
  Neuroblastoma
  Opioid dependence
  Paracoccidioidomycosis
  Paraplegia
  Parkinson disease
  Psoriasis
  Tuberculosis
  Vitiligo
  Alcohol dependence
  Asperger syndrome
  Cholestasis
  Chronic graft versus host disease
  Chronic obstructive pulmonary disease
  Lung cancer
  Lung carcinoma
  Moyamoya disease
  Neoplasm
  Primary cutaneous T-cell lymphoma
  Amyotrophic lateral sclerosis
  Stroke
• UniProt ID: NEUL_HUMAN
• PDB ID: 5LUZ; 5LV0
• EC Number: 3.4.24.16
• Pfam ID: PF01432
• Sequence:
  MIARCLLAVRSLRRVGGSRILLRMTLGREVMSPLQAMSSYTVAGRNVLRWDLSPEQIKTR
  TEELIVQTKQVYDAVGMLGIEEVTYENCLQALADVEVKYIVERTMLDFPQHVSSDKEVRA
  ASTEADKRLSRFDIEMSMRGDIFERIVHLQETCDLGKIKPEARRYLEKSIKMGKRNGLHL
  PEQVQNEIKSMKKRMSELCIDFNKNLNEDDTFLVFSKAELGALPDDFIDSLEKTDDDKYK
  ITLKYPHYFPVMKKCCIPETRRRMEMAFNTRCKEENTIILQQLLPLRTKVAKLLGYSTHA
  DFVLEMNTAKSTSRVTAFLDDLSQKLKPLGEAEREFILNLKKKECKDRGFEYDGKINAWD
  LYYYMTQTEELKYSIDQEFLKEYFPIEVVTEGLLNTYQELLGLSFEQMTDAHVWNKSVTL
  YTVKDKATGEVLGQFYLDLYPREGKYNHAACFGLQPGCLLPDGSRMMAVAALVVNFSQPV
  AGRPSLLRHDEVRTYFHEFGHVMHQICAQTDFARFSGTNVETDFVEVPSQMLENWVWDVD
  SLRRLSKHYKDGSPIADDLLEKLVASRLVNTGLLTLRQIVLSKVDQSLHTNTSLDAASEY
  AKYCSEILGVAATPGTNMPATFGHLAGGYDGQYYGYLWSEVFSMDMFYSCFKKEGIMNPE
  VGMKYRNLILKPGGSLDGMDMLHNFLKREPNQKAFLMSRGLHAP
• Function: Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1.
• KEGG Pathway: Renin-angiotensin system (hsa04614)
• Reactome Pathway: Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot-Marie-Tooth disease type 2	DISR30O9	Definitive	Genetic Variation	[1]
Chromosomal disorder	DISM5BB5	Definitive	Biomarker	[2]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[7]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[6]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[6]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[9]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[10]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[11]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[13]
Neuralgia	DISWO58J	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Opioid dependence	DIS6WEHK	Strong	Biomarker	[16]
Paracoccidioidomycosis	DIS88F55	Strong	Biomarker	[17]
Paraplegia	DISSKWBI	Strong	Genetic Variation	[18]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[19]
Psoriasis	DIS59VMN	Strong	Altered Expression	[20]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[17]
Vitiligo	DISR05SL	Strong	Biomarker	[21]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[22]
Asperger syndrome	DIS7IBSP	moderate	Biomarker	[23]
Cholestasis	DISDJJWE	moderate	Biomarker	[20]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[24]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[25]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[26]
Lung carcinoma	DISTR26C	moderate	Genetic Variation	[26]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[27]
Neoplasm	DISZKGEW	moderate	Biomarker	[28]
Primary cutaneous T-cell lymphoma	DIS35WVW	Disputed	Biomarker	[15]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[29]
Stroke	DISX6UHX	Limited	Biomarker	[30]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Neurolysin, mitochondrial (NLN).	[31]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Neurolysin, mitochondrial (NLN).	[43]

16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neurolysin, mitochondrial (NLN).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurolysin, mitochondrial (NLN).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neurolysin, mitochondrial (NLN).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neurolysin, mitochondrial (NLN).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neurolysin, mitochondrial (NLN).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neurolysin, mitochondrial (NLN).	[37]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Neurolysin, mitochondrial (NLN).	[38]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Neurolysin, mitochondrial (NLN).	[39]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neurolysin, mitochondrial (NLN).	[40]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Neurolysin, mitochondrial (NLN).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neurolysin, mitochondrial (NLN).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neurolysin, mitochondrial (NLN).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neurolysin, mitochondrial (NLN).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neurolysin, mitochondrial (NLN).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Neurolysin, mitochondrial (NLN).	[47]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Neurolysin, mitochondrial (NLN).	[48]

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