Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEAID7)

• DTT Name: Trypanosoma Cruzipain (Trypano CYSP)
• Synonyms: Cruzaine; Major cysteine proteinase
• Gene Name: Trypano CYSP
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: CYSP_TRYCR
• TTD ID: T30372
• EC Number: EC 3.4.22.51
• Sequence:
  MSGWARALLLAAVLVVMACLVPAATASLHAEETLTSQFAEFKQKHGRVYESAAEEAFRLS
  VFRENLFLARLHAAANPHATFGVTPFSDLTREEFRSRYHNGAAHFAAAQERARVPVKVEV
  VGAPAAVDWRARGAVTAVKDQGQCGSCWAFSAIGNVECQWFLAGHPLTNLSEQMLVSCDK
  TDSGCSGGLMNNAFEWIVQENNGAVYTEDSYPYASGEGISPPCTTSGHTVGATITGHVEL
  PQDEAQIAAWLAVNGPVAVAVDASSWMTYTGGVMTSCVSEQLDHGVLLVGYNDSAAVPYW
  IIKNSWTTQWGEEGYIRIAKGSNQCLVKEEASSAVVGGPGPTPEPTTTTTTSAPGPSPSY
  FVQMSCTDAACIVGCENVTLPTGQCLLTTSGVSAIVTCGAETLTEEVFLTSTHCSGPSVR
  SSVPLNKCNRLLRGSVEFFCGSSSSGRLADVDRQRRHQPYHSRHRRL
• Function: The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TRICLABENDAZOLE	DMPWGBR	Helminth infection	1F90.0	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MANIDIPINE	DMJPGUA	N. A.	N. A.	Phase 3	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-755507	DMPWBNU	N. A.	N. A.	Terminated	[2]

27 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3Z)-1H-indole-2,3-dione 3-thiosemicarbazone	DMI9N8G	Discovery agent	N.A.	Investigative	[3]
1-(1-(3-nitrophenyl)propylidene)thiosemicarbazide	DM0XNMP	Discovery agent	N.A.	Investigative	[4]
1-(3,4-dihydronaphthalen-1-yl)ethanone	DM5C7I8	Discovery agent	N.A.	Investigative	[4]
1-(3-Methoxy-benzyl)-5-methyl-1H-indole-2,3-dione	DM30M9H	Discovery agent	N.A.	Investigative	[3]
1-(bis(3-bromophenyl)methylene)thiosemicarbazide	DMTZ71K	Discovery agent	N.A.	Investigative	[4]
2-(cycloheptylamino)-2-oxoethyl 2-aminonicotinate	DMQ9ODG	Discovery agent	N.A.	Investigative	[5]
2-(trifluoromethyl)benzaldehyde thiosemicarbazone	DMWAKFM	Discovery agent	N.A.	Investigative	[6]
2-methoxy-1-naphthaldehyde thiosemicarbazone	DMH76C5	Discovery agent	N.A.	Investigative	[6]
3',4'-dichloroacetophenonethiosemicarbazone	DMS1QIJ	Discovery agent	N.A.	Investigative	[7]
3'-bromopropiophenonethiosemicarbazone	DMK7D8N	Discovery agent	N.A.	Investigative	[7]
3,4-dichlorobenzaldehyde thiosemicarbazone	DMUSPIC	Discovery agent	N.A.	Investigative	[6]
3,5-dichlorobenzaldehyde thiosemicarbazone	DMPVI9W	Discovery agent	N.A.	Investigative	[6]
3-(trifluoromethyl)benzaldehyde thiosemicarbazone	DM2YVA1	Discovery agent	N.A.	Investigative	[6]
3-amino-5-(furan-2-yl)biphenyl-2,4-dicarbonitrile	DM6Y2KW	Discovery agent	N.A.	Investigative	[2]
3-chloro-N-(4-(phenyldiazenyl)phenyl)benzamide	DMBVCLY	Discovery agent	N.A.	Investigative	[2]
5-(3,4-dichlorophenyl)-1H-pyrazol-3-ol	DMRF0PS	Discovery agent	N.A.	Investigative	[2]
5-(4-bromophenyl)-2-furaldehyde thiosemicarbazone	DMT4856	Discovery agent	N.A.	Investigative	[6]
5-Chloro-1-(4-chloro-benzyl)-1H-indole-2,3-dione	DMIH7W1	Discovery agent	N.A.	Investigative	[3]
Benzoyl-Arginine-Alanine-Methyl Ketone	DMC7TNF	Discovery agent	N.A.	Investigative	[8]
GNF-PF-4478	DMCDU8K	Discovery agent	N.A.	Investigative	[9]
K-777	DMIFCMW	Discovery agent	N.A.	Investigative	[10]
N1,N4-bis(5-chloro-2-methylphenyl)succinamide	DMRO7JX	Discovery agent	N.A.	Investigative	[2]
Vinylsulphones	DMNFVO7	Infection of P. falciparum	1F40	Investigative	[11]
VITAMIN K2	DMJB3E1	Discovery agent	N.A.	Investigative	[1]
WRR-112	DMP761U	Discovery agent	N.A.	Investigative	[8]
WRR-204	DMRVAH1	Discovery agent	N.A.	Investigative	[8]
WRR-99	DM8ZA6K	Discovery agent	N.A.	Investigative	[8]

References

• [1] Colloid formation by drugs in simulated intestinal fluid. J Med Chem. 2010 May 27;53(10):4259-65.
• [2] Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J Med Chem. 2010 Jan 14;53(1):37-51.
• [3] Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3527-30.
• [4] Design, synthesis, and biochemical evaluation of novel cruzain inhibitors with potential application in the treatment of Chagas' disease. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4405-9.
• [5] Divergent modes of enzyme inhibition in a homologous structure-activity series. J Med Chem. 2009 Aug 27;52(16):5005-8.
• [6] Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruz... J Med Chem. 2002 Jun 20;45(13):2695-707.
• [7] Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorg Med Chem. 2010 Nov 15;18(22):7826-35.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem. 2010 Jul 8;53(13):4891-905.
• [10] Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21.
• [11] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.