Target Information

Target General Information

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Target ID

T77195 (Former ID: TTDS00469)

Target Name

NADH dehydrogenase (MT-ND3)

Synonyms

ND; NADH-ubiquinone oxidoreductase; NADH; MTND; MT-ND3; MT-ND

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Gene Name

MT-ND3

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Parkinsonism [ICD-11: 8A00]

Function

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in thetransfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.

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BioChemical Class

NADH/NADPH oxidoreductase

UniProt ID

NU3M_HUMAN

EC Number

EC 7.1.1.2

Sequence

MNFALILMINTLLALLLMIITFWLPQLNGYMEKSTPYECGFDPMSPARVPFSMKFFLVAI
TFLLFDLEIALLLPLPWALQTTNLPLMVMSSLLLIIILALSLAYEWLQKGLDWTE

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3D Structure

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PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

NADH

Drug Info

Approved

Parkinson disease

[2], [3]

Mode of Action

[+] 2 Modes of Action

Binder

[+] 1 Binder drugs

NADH

Drug Info

[1]

Inhibitor

[+] 3 Inhibitor drugs

6-Thiophen-2-yl-imidazo[2,1-b]thiazole

Drug Info

[4]

6-Thiophen-3-yl-imidazo[2,1-b]thiazole

Drug Info

[4]

N-Formylmethionine

Drug Info

[5]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Oxidative phosphorylation	hsa00190	Affiliated Target
Class: Metabolism => Energy metabolism	Pathway Hierarchy
Thermogenesis	hsa04714	Affiliated Target
Class: Organismal Systems => Environmental adaptation	Pathway Hierarchy
Retrograde endocannabinoid signaling	hsa04723	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy

Degree	48	Degree centrality	5.16E-03	Betweenness centrality	2.53E-05
Closeness centrality	1.96E-01	Radiality	1.34E+01	Clustering coefficient	8.33E-01
Neighborhood connectivity	5.44E+01	Topological coefficient	4.25E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 3 KEGG Pathways

Oxidative phosphorylation

Metabolic pathways

Parkinson's disease

WikiPathways

[+] 3 WikiPathways

Oxidative phosphorylation

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Electron Transport Chain

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Mechanism of cadmium-decreased glucuronidation in the rat. Biochem Pharmacol. 1992 Dec 1;44(11):2139-47.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4487).

REF 3

Drug information of NADH, 2008. eduDrugs.

REF 4

Thienylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase. J Med Chem. 1995 Mar 31;38(7):1090-7.

REF 5

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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