Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVTX4N)

• DTT Name: Bacterial Fatty acid synthetase I (Bact inhA)
• Synonyms: Enoyl-[acyl-carrier-protein] reductase [NADH]; Bacterial InhA
• Gene Name: Bact inhA
• DTT Type: Successful target; [1]
• Related Disease:
  HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]
  Mycobacterium infection [ICD-11: 1B10-1B21]
• BioChemical Class: CH-CH donor oxidoreductase
• UniProt ID: INHA_MYCTU
• TTD ID: T79068
• Sequence:
  MTGLLDGKRILVSGIITDSSIAFHIARVAQEQGAQLVLTGFDRLRLIQRITDRLPAKAPL
  LELDVQNEEHLASLAGRVTEAIGAGNKLDGVVHSIGFMPQTGMGINPFFDAPYADVSKGI
  HISAYSYASMAKALLPIMNPGGSIVGMDFDPSRAMPAYNWMTVAKSALESVNRFVAREAG
  KYGVRSNLVAAGPIRTLAMSAIVGGALGEEAGAQIQLLEEGWDQRAPIGWNMKDATPVAK
  TVCALLSDWLPATTGDIIYADGGAHTQLL
• Function: Involved in the resistance against the antituberculosis drugs isoniazid and ethionamide.
• BioCyc Pathway: MetaCyc:G185E-5668-MON

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethionamide	DM8K3EI	Tuberculosis	1B10-1B1Z	Approved	[2], [3]
Isoniazid	DM5JVS3	Tuberculosis	1B10-1B1Z	Approved	[1], [4], [5]
Prothionamide	DMX0EZJ	Tuberculosis	1B10-1B1Z	Approved	[2], [6]
Pyrazinamide	DM4IF32	Mycobacterium infection	1B10-1B21	Approved	[7]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AFN-1720	DM6AJKC	Bacterial infection	1A00-1C4Z	Phase 2	[8]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MMV00/0053	DMF27BS	Malaria	1F40-1F45	Terminated	[9]

43 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(4-benzylpiperidin-1-yl)(2-fluorophenyl)methanone	DMGVDEL	Discovery agent	N.A.	Investigative	[10]
(4-benzylpiperidin-1-yl)(3-chlorophenyl)methanone	DMEQZ5M	Discovery agent	N.A.	Investigative	[10]
(4-benzylpiperidin-1-yl)(m-tolyl)methanone	DMS16CO	Discovery agent	N.A.	Investigative	[10]
(4-benzylpiperidin-1-yl)(p-tolyl)methanone	DMJ81M3	Discovery agent	N.A.	Investigative	[11], [10]
(4-phenylpiperazin-1-yl)(p-tolyl)methanone	DM0NTA3	Discovery agent	N.A.	Investigative	[10]
2-(2-aminophenoxy)-5-hexylphenol	DMM9A8G	Discovery agent	N.A.	Investigative	[12]
2-(3-aminophenoxy)-5-hexylphenol	DMC6E8R	Discovery agent	N.A.	Investigative	[12]
2-(4,6-dimethoxypyrimidin-2-yloxy)-5-hexylphenol	DM1UBGQ	Discovery agent	N.A.	Investigative	[12]
2-(4-aminophenoxy)-5-hexylphenol	DMP0GI8	Discovery agent	N.A.	Investigative	[12]
2-(4-hexyl-2-methoxyphenoxy)pyrimidine	DM05HBC	Discovery agent	N.A.	Investigative	[12]
2-bromo-4-methylphenyl 2-nitrobenzoate	DMJ0368	Discovery agent	N.A.	Investigative	[13]
2-Hexadecynoic acid	DMTFIPZ	Discovery agent	N.A.	Investigative	[14]
2-nitro-N-(2,4,5-trichlorophenyl)benzamide	DMRZK9A	Discovery agent	N.A.	Investigative	[13]
4-(2-Thienyl)-1-(4-Methylbenzyl)-1h-Imidazole	DMX681M	Discovery agent	N.A.	Investigative	[15]
4-chloro-N-(2,5-dichlorophenyl)-3-nitrobenzamide	DMHL9V3	Discovery agent	N.A.	Investigative	[13]
5-hexyl-2-(2-nitrophenoxy)phenol	DM0OJZF	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(3-nitrophenoxy)phenol	DM7EBQL	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(4-nitrophenoxy)phenol	DMNBLPA	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(pyrazin-2-yloxy)phenol	DM9263J	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(pyridin-2-yloxy)phenol	DMLIMOP	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(pyridin-3-yloxy)phenol	DMHZT1S	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(pyridin-4-yloxy)phenol	DMP6U3L	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-(pyrimidin-2-yloxy)phenol	DMNYOV3	Discovery agent	N.A.	Investigative	[12]
5-hexyl-2-phenoxyphenol	DMHNRXT	Discovery agent	N.A.	Investigative	[12]
5-octyl-2-phenoxyphenol	DMAXHEU	Discovery agent	N.A.	Investigative	[16]
5-PENTYL-2-PHENOXYPHENOL	DMKHFV4	Discovery agent	N.A.	Investigative	[11]
Beta-D-Glucose	DM5IHYP	Discovery agent	N.A.	Investigative	[15]
C16-Fatty-Acyl-Substrate-Mimic	DM23KNC	Discovery agent	N.A.	Investigative	[15]
Diclosan	DMO3KU5	Discovery agent	N.A.	Investigative	[15]
Genz-10850	DMB70WC	Discovery agent	N.A.	Investigative	[15]
Indole Naphthyridinone	DMB4ZNW	Discovery agent	N.A.	Investigative	[15]
N-(2,4-dichlorophenyl)-2-nitrobenzamide	DM5COQ9	Discovery agent	N.A.	Investigative	[13]
N-(2,4-dichlorophenyl)-4-methyl-3-nitrobenzamide	DMHJOBQ	Discovery agent	N.A.	Investigative	[13]
N-(2,4-dimethylphenyl)-2-nitrobenzamide	DMFZAS9	Discovery agent	N.A.	Investigative	[13]
N-(2,5-dichlorophenyl)-4-methoxy-3-nitrobenzamide	DMUVSM1	Discovery agent	N.A.	Investigative	[13]
N-(2-(4-hexyl-2-hydroxyphenoxy)phenyl)acetamide	DM57GQN	Discovery agent	N.A.	Investigative	[12]
N-(3,5-dichlorophenyl)-2-nitrobenzamide	DMDNUCL	Discovery agent	N.A.	Investigative	[13]
N-(3,5-dichlorophenyl)-4-methoxy-3-nitrobenzamide	DM8DAGL	Discovery agent	N.A.	Investigative	[13]
N-(3,5-dimethoxyphenyl)-4-methyl-2-nitrobenzamide	DM43QHV	Discovery agent	N.A.	Investigative	[13]
N-(3-(4-hexyl-2-hydroxyphenoxy)phenyl)acetamide	DMOCZVB	Discovery agent	N.A.	Investigative	[12]
N-(4-(4-hexyl-2-hydroxyphenoxy)phenyl)acetamide	DMQDI5H	Discovery agent	N.A.	Investigative	[12]
N-(4-(diethylamino)phenyl)-2-nitrobenzamide	DMZAOVG	Discovery agent	N.A.	Investigative	[13]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[15]

References

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• [2] Mechanism of thioamide drug action against tuberculosis and leprosy. J Exp Med. 2007 Jan 22;204(1):73-8.
• [3] Calcium-activated conductance in skate electroreceptors: current clamp experiments. J Gen Physiol. 1977 Feb;69(2):121-43.
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• [6] Ability of the Ca2+ ionophores A23187 and ionomycin to mimic some of the effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on hydroperoxide production, ornithine decarboxylase activity, and DNA synthesis in mouse epidermis in vivo. Cancer Res. 1990 Sep 15;50(18):5806-12.
• [7] Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
• [8] Affinium Pharmaceuticals Announces the Initiation of a Phase 1 Intravenous Clinical Trial of a New Antibiotic Prodrug, and the Closing of a Follow-on Financing Round. PR Newswire Sep. 4, 2013 10:16 PM.
• [9] SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase. IUBMB Life. 2010 Mar;62(3):204-13.
• [10] Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. Bioorg Med Chem. 2007 Nov 1;15(21):6649-58.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] Synthesis and in vitro antimycobacterial activity of B-ring modified diaryl ether InhA inhibitors. Bioorg Med Chem Lett. 2008 May 15;18(10):3029-33.
• [13] Discovery of potential new InhA direct inhibitors based on pharmacophore and 3D-QSAR analysis followed by in silico screening. Eur J Med Chem. 2009 Sep;44(9):3718-30.
• [14] 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. Bioorg Med Chem. 2010 Nov 1;18(21):7475-85.
• [15] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [16] Natural products, small molecules, and genetics in tuberculosis drug development. J Med Chem. 2008 May 8;51(9):2606-12.