Target Information

Target General Information

Target ID

T53748 (Former ID: TTDS00235)

Target Name

Plasmodium Enoyl-ACP reductase (Malaria fabI)

Synonyms

fabI; NADH-dependent enoyl-ACP reductase; Enoyl-acyl-carrier protein reductase; Enoyl-acyl carrier reductase; Enoyl-acyl carrier protein reductase; Enoyl-ACP reductase FabI

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Gene Name

Malaria fabI

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Malaria [ICD-11: 1F40-1F45]

Function

Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.

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BioChemical Class

CH-CH donor oxidoreductase

UniProt ID

Q965D5_PLAFA

EC Number

EC 1.3.1.9

Sequence

MNKISQRLLFLFLHFYTTVCFIQNNTQKTFHNVLQNEQIRGKEKAFYRKEKRENIFIGNK
MKHVHNMNNTHNNNHYMEKEEQDASNINKIKEENKNEDICFIAGIGDTNGYGWGIAKELS
KRNVKIIFGIWPPVYNIFMKNYKNGKFDNDMIIDKDKKMNILDMLPFDASFDTANDIDEE
TKNNKRYNMLQNYPIEDVANLIHQKYGKINMLVHSLANAKEVQKDLLNTSRKGYLDALSK
SSYSLISLCKYFVNIMKPQSSIISLTYHASQKVVPGYGGGMSSAKAALESDTRVLAYHLG
RNYNIRINTISAGPLKSRAATAINKLNNTYENNTNQNKNRNSHDVHNIMNNSGEKEEKKN
SASQNYTFIDYAIEYSEKYAPLRQKLLSTDIGSVASFLLSRESRAITGQTIYVDNGLNIM
FLPDDIYRNENE

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Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

Triclosan

Drug Info

Approved

Malaria

[2]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

Epigallocatechin gallate

Drug Info

Phase 3

Hepatic fibrosis

[3], [4], [5], [6]

Mode of Action

[+] 2 Modes of Action

Binder

[+] 1 Binder drugs

Triclosan

Drug Info

[1], [7], [8], [9]

Inhibitor

[+] 33 Inhibitor drugs

Epigallocatechin gallate

Drug Info

[10]

(-)-CATECHINGALLATE

Drug Info

[11]

2-(2,4-dichlorophenoxy)-5-(2-methylbutyl)phenol

Drug Info

[12]

2-(2,4-dichlorophenoxy)-5-(3-phenylpropyl)phenol

Drug Info

[13]

2-(2,4-dichlorophenoxy)-5-ethylphenol

Drug Info

[13]

2-(2,4-dichlorophenoxy)-5-isobutylphenol

Drug Info

[12]

2-(2,4-dichlorophenoxy)-5-isopentylphenol

Drug Info

[12]

2-(2,4-dichlorophenoxy)-5-methylphenol

Drug Info

[13]

2-(2,4-dichlorophenoxy)-5-phenethylphenol

Drug Info

[12]

2-(2,4-dichlorophenoxy)-5-propylphenol

Drug Info

[13]

2-(2-((benzylamino)methyl)phenoxy)-5-chlorophenol

Drug Info

[14]

2-(4-chloro-2-hydroxyphenoxy)benzenaminium

Drug Info

[12]

3,7,3',4'-TETRAHYDROXYFLAVONE

Drug Info

[11]

3,7-dihydroxy-flavone

Drug Info

[11]

3-chloro-4-(4-chloro-2-hydroxyphenoxy)benzamide

Drug Info

[15]

4-(2,4-dichloro-phenoxy)-2'-methyl-biphenyl-3-ol

Drug Info

[13]

4-(2,4-dichloro-phenoxy)-4'-fluoro-biphenyl-3-ol

Drug Info

[13]

4-(2,4-dichloro-phenoxy)-biphenyl-3-ol

Drug Info

[13]

4-(2,4-dichlorophenoxy)-3'-methylbiphenyl-3-ol

Drug Info

[12]

4-(2,4-dichlorophenoxy)-4'-methylbiphenyl-3-ol

Drug Info

[12]

4-(2-Thienyl)-1-(4-Methylbenzyl)-1h-Imidazole

Drug Info

[16]

5-benzyl-2-(2,4-dichlorophenoxy)phenol

Drug Info

[12]

5-butyl-2-(2,4-dichlorophenoxy)phenol

Drug Info

[12]

5-chloro-2-(2-chloro-4-hydroxyphenoxy)phenol

Drug Info

[15]

Beta-D-Glucose

Drug Info

[16]

BUTEIN

Drug Info

[10]

Diazaborines

Drug Info

[8]

GALLOCATECHIN GALLATE

Drug Info

[11]

ISORHAMNETIN

Drug Info

[11]

MORIN

Drug Info

[11]

Nicotinamide-Adenine-Dinucleotide

Drug Info

[16]

OROIDIN

Drug Info

[17]

Thiolactomycin

Drug Info

[1]

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 Similarity Proteins

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 Similarity Proteins

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

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(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

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.

REF 2

The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.

REF 3

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: 7002).

REF 4

The green tea polyphenol (2)-epigallocatechin-3-gallate (EGCG) is not a beta-secretase inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1408-14.

REF 5

Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse. Toxicol Sci. 2003 Dec;76(2):262-70.

REF 6

Prolyl endopeptidase inhibitors from green tea. Arch Pharm Res. 2001 Aug;24(4):292-6.

REF 7

The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51.

REF 8

Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97.

REF 9

Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.

REF 10

Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR). J Med Chem. 2007 Feb 22;50(4):765-75.

REF 11

Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53.

REF 12

Design and in silico screening of combinatorial library of antimalarial analogs of triclosan inhibiting Plasmodium falciparum enoyl-acyl carrier pr... Eur J Med Chem. 2009 Jul;44(7):3009-19.

REF 13

X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalar... J Biol Chem. 2007 Aug 31;282(35):25436-44.

REF 14

Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2'-substituted triclosan der... Bioorg Med Chem Lett. 2006 Apr 15;16(8):2163-9.

REF 15

Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. ... Bioorg Med Chem Lett. 2005 Dec 1;15(23):5247-52.

REF 16

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

REF 17

Marine natural products from the Turkish sponge Agelas oroides that inhibit the enoyl reductases from Plasmodium falciparum, Mycobacterium tubercul... Bioorg Med Chem. 2007 Nov 1;15(21):6834-45.

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