Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Trypanosoma Trypanothione reductase (Trypano TPR)
• Synonyms: TRYR; TPR; Parasite-specific trypanothione reductase; N(1),N(8)-bis(glutathionyl)spermidine reductase
• Gene Name: Trypano TPR
• DTT Type: Successful target; [1]
• BioChemical Class: Sulfur donor oxidoreductase
• UniProt ID: TYTR_TRYBB
• TTD ID: T99616
• EC Number: EC 1.8.1.12
• Sequence:
  MSKIFDLVVIGAGSGGLEAGWNAATLYKKRVAVIDVQTHHGPPHYAALGGTCVNVGCVPK
  KLMVTGAQYMDHLRESAGFGWEFDGSSVKANWKKLIAAKNEAVLDINKSYEGMFNDTEGL
  DFFLGWGSLESKNVVVVRETADPKSAVKERLQADHILLATGSWPQMPAIPGVEHCISSNE
  AFYLPEPPRRVLTVGGGFISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEVTK
  QLTANGIEIMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNVG
  VKLTPKGGVQVDEFSRTNVPNIYAIGDITDRLMLTPVAINEGAALVDTVFGNKPRKTDHT
  RVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTPLMHNISGSKYKKFVAKIVTNHS
  DGTVLGVHLLGDGAPEIIQAVGVCLRLNAKISDFYNTIGVHPTSAEELCSMRTPSYYYLK
  GEKMETLPESSL
• Function: Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[1]
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[2]

8 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(2'-chlorophenyl)penta-1,4-dien-3-one	DMKTZSY	Discovery agent	N.A.	Investigative	[3]
CEPHARANTINE	DMCE3NA	Discovery agent	N.A.	Investigative	[4]
CONESSINE	DM4VYP0	Discovery agent	N.A.	Investigative	[4]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[5]
Maleic Acid	DM4L0R7	Discovery agent	N.A.	Investigative	[6]
N-(5-chloro-2-(phenylthio)phenyl)butyramide	DMHZ256	Discovery agent	N.A.	Investigative	[7]
N1,N2-bis(dihydrocaffeoyl)spermine	DMSDVGQ	Discovery agent	N.A.	Investigative	[4]
Trypanothione	DMDUGQ1	Discovery agent	N.A.	Investigative	[5]

References

• [1] 8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase. Mem Inst Oswaldo Cruz. 2003 Jun;98(4):565-8.
• [2] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [3] Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem. 2005 Nov 17;48(23):7400-10.
• [4] The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors. Bioorg Med Chem. 2008 Jul 15;16(14):6689-95.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class ... J Med Chem. 2005 Dec 15;48(25):8087-97.