Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNX2CS)

• DTT 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
• Gene Name: Malaria fabI
• DTT Type: Successful target; [1]
• Related Disease: Malaria [ICD-11: 1F40-1F45]
• BioChemical Class: CH-CH donor oxidoreductase
• UniProt ID: Q965D5_PLAFA
• TTD ID: T53748
• EC Number: EC 1.3.1.9
• Sequence:
  MNKISQRLLFLFLHFYTTVCFIQNNTQKTFHNVLQNEQIRGKEKAFYRKEKRENIFIGNK
  MKHVHNMNNTHNNNHYMEKEEQDASNINKIKEENKNEDICFIAGIGDTNGYGWGIAKELS
  KRNVKIIFGIWPPVYNIFMKNYKNGKFDNDMIIDKDKKMNILDMLPFDASFDTANDIDEE
  TKNNKRYNMLQNYPIEDVANLIHQKYGKINMLVHSLANAKEVQKDLLNTSRKGYLDALSK
  SSYSLISLCKYFVNIMKPQSSIISLTYHASQKVVPGYGGGMSSAKAALESDTRVLAYHLG
  RNYNIRINTISAGPLKSRAATAINKLNNTYENNTNQNKNRNSHDVHNIMNNSGEKEEKKN
  SASQNYTFIDYAIEYSEKYAPLRQKLLSTDIGSVASFLLSRESRAITGQTIYVDNGLNIM
  FLPDDIYRNENE
• 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.

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[1], [2], [3], [4]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[5]

36 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-CATECHINGALLATE	DMZOGSK	Discovery agent	N.A.	Investigative	[6]
2-(2,4-dichlorophenoxy)-5-(2-methylbutyl)phenol	DM4XL8Z	Discovery agent	N.A.	Investigative	[7]
2-(2,4-dichlorophenoxy)-5-(3-phenylpropyl)phenol	DME3FUD	Discovery agent	N.A.	Investigative	[8]
2-(2,4-dichlorophenoxy)-5-ethylphenol	DMPSR1O	Discovery agent	N.A.	Investigative	[8]
2-(2,4-dichlorophenoxy)-5-isobutylphenol	DMKOFRE	Discovery agent	N.A.	Investigative	[7]
2-(2,4-dichlorophenoxy)-5-isopentylphenol	DME0LZ2	Discovery agent	N.A.	Investigative	[7]
2-(2,4-dichlorophenoxy)-5-methylphenol	DM1L3US	Discovery agent	N.A.	Investigative	[8]
2-(2,4-dichlorophenoxy)-5-phenethylphenol	DM6ZNR3	Discovery agent	N.A.	Investigative	[7]
2-(2,4-dichlorophenoxy)-5-propylphenol	DMKP974	Discovery agent	N.A.	Investigative	[8]
2-(2-((benzylamino)methyl)phenoxy)-5-chlorophenol	DMGZKCT	Discovery agent	N.A.	Investigative	[9]
2-(4-amino-2-chlorophenoxy)-5-chlorophenol	DMUANX1	Discovery agent	N.A.	Investigative	[10]
2-(4-chloro-2-hydroxyphenoxy)benzenaminium	DMBHFIM	Discovery agent	N.A.	Investigative	[7]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Discovery agent	N.A.	Investigative	[6]
3,7-dihydroxy-flavone	DMH04P7	Discovery agent	N.A.	Investigative	[6]
3-chloro-4-(4-chloro-2-hydroxyphenoxy)benzamide	DMZ5JFG	Discovery agent	N.A.	Investigative	[10]
4-(2,4-dichloro-phenoxy)-2'-methyl-biphenyl-3-ol	DMPKE6G	Discovery agent	N.A.	Investigative	[8]
4-(2,4-dichloro-phenoxy)-4'-fluoro-biphenyl-3-ol	DMAK789	Discovery agent	N.A.	Investigative	[8]
4-(2,4-dichloro-phenoxy)-biphenyl-3-ol	DMB96SY	Discovery agent	N.A.	Investigative	[8]
4-(2,4-dichlorophenoxy)-3'-methylbiphenyl-3-ol	DMY6GWF	Discovery agent	N.A.	Investigative	[7]
4-(2,4-dichlorophenoxy)-3-hydroxybenzonitrile	DMS7POY	Discovery agent	N.A.	Investigative	[8]
4-(2,4-dichlorophenoxy)-4'-methylbiphenyl-3-ol	DMRPVO3	Discovery agent	N.A.	Investigative	[7]
4-(2-Thienyl)-1-(4-Methylbenzyl)-1h-Imidazole	DMX681M	Discovery agent	N.A.	Investigative	[11]
5-benzyl-2-(2,4-dichlorophenoxy)phenol	DM5MJ3I	Discovery agent	N.A.	Investigative	[7]
5-butyl-2-(2,4-dichlorophenoxy)phenol	DMCNU6I	Discovery agent	N.A.	Investigative	[7]
5-chloro-2-(2-chloro-4-hydroxyphenoxy)phenol	DMDZ8NA	Discovery agent	N.A.	Investigative	[10]
5-chloro-2-(2-chloro-4-nitrophenoxy)phenol	DMAJ8BS	Discovery agent	N.A.	Investigative	[10]
Beta-D-Glucose	DM5IHYP	Discovery agent	N.A.	Investigative	[11]
BUTEIN	DM8E54P	Discovery agent	N.A.	Investigative	[5]
Diazaborines	DM5UFZX	Discovery agent	N.A.	Investigative	[3]
GALLOCATECHIN GALLATE	DMX2084	Discovery agent	N.A.	Investigative	[6]
Indole Naphthyridinone	DMB4ZNW	Discovery agent	N.A.	Investigative	[11]
ISORHAMNETIN	DMQ4Z6E	Discovery agent	N.A.	Investigative	[6]
Morin	DM2OGZ5	Discovery agent	N.A.	Investigative	[6]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[11]
OROIDIN	DMA2DQT	Discovery agent	N.A.	Investigative	[12]
Thiolactomycin	DMBAWDG	Malaria	1F40-1F45	Investigative	[1]

References

• [1] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [2] The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51.
• [3] Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97.
• [4] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [5] Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR). J Med Chem. 2007 Feb 22;50(4):765-75.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] 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.