Target Information

Target General Information

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Target ID

T65291 (Former ID: TTDS00053)

Target Name

Fatty aldehyde dehydrogenase (ALDH3A2)

Synonyms

Microsomal aldehyde dehydrogenase; Aldehyde dehydrogenase family 3 member A2; Aldehyde dehydrogenase 10; ALDH10

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Gene Name

ALDH3A2

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Substance abuse [ICD-11: 6C40]

Function

Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.

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BioChemical Class

Aldehyde/oxo donor oxidoreductase

UniProt ID

AL3A2_HUMAN

EC Number

EC 1.2.1.3

Sequence

MELEVRRVRQAFLSGRSRPLRFRLQQLEALRRMVQEREKDILTAIAADLCKSEFNVYSQE
VITVLGEIDFMLENLPEWVTAKPVKKNVLTMLDEAYIQPQPLGVVLIIGAWNYPFVLTIQ
PLIGAIAAGNAVIIKPSELSENTAKILAKLLPQYLDQDLYIVINGGVEETTELLKQRFDH
IFYTGNTAVGKIVMEAAAKHLTPVTLELGGKSPCYIDKDCDLDIVCRRITWGKYMNCGQT
CIAPDYILCEASLQNQIVWKIKETVKEFYGENIKESPDYERIINLRHFKRILSLLEGQKI
AFGGETDEATRYIAPTVLTDVDPKTKVMQEEIFGPILPIVPVKNVDEAINFINEREKPLA
LYVFSHNHKLIKRMIDETSSGGVTGNDVIMHFTLNSFPFGGVGSSGMGAYHGKHSFDTFS
HQRPCLLKSLKREGANKLRYPPNSQSKVDWGKFFLLKRFNKEKLGLLLLTFLGIVAAVLV
KAEYY

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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

Disulfiram

Drug Info

Approved

Alcohol dependence

[2], [3]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

NPS 1776

Drug Info

Discontinued in Phase 2

Epilepsy

[4]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 4 Inhibitor drugs

Disulfiram

Drug Info

[1]

Aloe-emodin

Drug Info

[6]

NSC-527035

Drug Info

[7]

S-methyl 4-methyl-4-morpholinopent-2-ynethioate

Drug Info

[8]

Modulator

[+] 1 Modulator drugs

NPS 1776

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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). 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 Tissue Distribution 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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

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 Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

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


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Glycolysis / Gluconeogenesis	hsa00010	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Ascorbate and aldarate metabolism	hsa00053	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Fatty acid degradation	hsa00071	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Valine, leucine and isoleucine degradation	hsa00280	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
Lysine degradation	hsa00310	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
Arginine and proline metabolism	hsa00330	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
Histidine metabolism	hsa00340	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
Tryptophan metabolism	hsa00380	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
beta-Alanine metabolism	hsa00410	Affiliated Target
Class: Metabolism => Metabolism of other amino acids	Pathway Hierarchy
Glycerolipid metabolism	hsa00561	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Pyruvate metabolism	hsa00620	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Pantothenate and CoA biosynthesis	hsa00770	Affiliated Target
Class: Metabolism => Metabolism of cofactors and vitamins	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	4	Degree centrality	4.30E-04	Betweenness centrality	6.05E-04
Closeness centrality	1.71E-01	Radiality	1.27E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.30E+01	Topological coefficient	2.93E-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

Co-Targets

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Co-Targets

Co-Targets Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.

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: 7168).

REF 3

Choosing the right medication for the treatment of alcoholism. Curr Psychiatry Rep. 2006 Oct;8(5):383-8.

REF 4

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010984)

REF 5

Diverse Mechanisms of Antiepileptic Drugs in the Development Pipeline. Epilepsy Res. 2006 June; 69(3): 273-294.

REF 6

Elgonica-Dimers A and B, Two Potent Alcohol Metabolism Inhibitory Constituents of Aloe arborescens J. Nat. Prod. 60(11):1180-1182 (1997).

REF 7

Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast... J Med Chem. 2010 Apr 8;53(7):2757-65.

REF 8

Aldehyde dehydrogenase inhibitors: alpha,beta-acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but i... Eur J Med Chem. 2008 May;43(5):906-16.

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