Target Information

Target General Infomation
Target ID
T30372
Former ID
TTDR00982
Target Name
Cruzipain
Synonyms
Congopain; Cruzaine; Cysteine proteinase cruzipain; Major cysteine proteinase
Target Type
Successful
Disease Helminth infection [ICD9: 001-139; ICD10: A00-B99]
Infection of P. falciparum [ICD9: 84; ICD10: B50-B54]
Function
The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
BioChemical Class
Peptidase
Target Validation
T30372
UniProt ID
P25779
EC Number
EC 3.4.22.51
Sequence
MSGWARALLLAAVLVVMACLVPAATASLHAEETLTSQFAEFKQKHGRVYESAAEEAFRLS
VFRENLFLARLHAAANPHATFGVTPFSDLTREEFRSRYHNGAAHFAAAQERARVPVKVEV
VGAPAAVDWRARGAVTAVKDQGQCGSCWAFSAIGNVECQWFLAGHPLTNLSEQMLVSCDK
TDSGCSGGLMNNAFEWIVQENNGAVYTEDSYPYASGEGISPPCTTSGHTVGATITGHVEL
PQDEAQIAAWLAVNGPVAVAVDASSWMTYTGGVMTSCVSEQLDHGVLLVGYNDSAAVPYW
IIKNSWTTQWGEEGYIRIAKGSNQCLVKEEASSAVVGGPGPTPEPTTTTTTSAPGPSPSY
FVQMSCTDAACIVGCENVTLPTGQCLLTTSGVSAIVTCGAETLTEEVFLTSTHCSGPSVR
SSVPLNKCNRLLRGSVEFFCGSSSSGRLADVDRQRRHQPYHSRHRRL
Drugs and Mode of Action
Drug(s) TRICLABENDAZOLE Drug Info Approved Helminth infection [551871]
MANIDIPINE Drug Info Phase 3 Discovery agent [521680]
L-755507 Drug Info Terminated Discovery agent [540554], [546489]
Inhibitor (3Z)-1H-indole-2,3-dione 3-thiosemicarbazone Drug Info [526832]
1-(1-(3-nitrophenyl)propylidene)thiosemicarbazide Drug Info [528258]
1-(3,4-dihydronaphthalen-1-yl)ethanone Drug Info [528258]
1-(3-Methoxy-benzyl)-5-methyl-1H-indole-2,3-dione Drug Info [526832]
1-(bis(3-bromophenyl)methylene)thiosemicarbazide Drug Info [528258]
2-(cycloheptylamino)-2-oxoethyl 2-aminonicotinate Drug Info [530281]
2-(trifluoromethyl)benzaldehyde thiosemicarbazone Drug Info [526354]
2-methoxy-1-naphthaldehyde thiosemicarbazone Drug Info [526354]
3',4'-dichloroacetophenonethiosemicarbazone Drug Info [531227]
3'-bromopropiophenonethiosemicarbazone Drug Info [531227]
3,4-dichlorobenzaldehyde thiosemicarbazone Drug Info [526354]
3,5-dichlorobenzaldehyde thiosemicarbazone Drug Info [526354]
3-(trifluoromethyl)benzaldehyde thiosemicarbazone Drug Info [526354]
3-amino-5-(furan-2-yl)biphenyl-2,4-dicarbonitrile Drug Info [530512]
3-chloro-N-(4-(phenyldiazenyl)phenyl)benzamide Drug Info [530512]
5-(3,4-dichlorophenyl)-1H-pyrazol-3-ol Drug Info [530512]
5-(4-bromophenyl)-2-furaldehyde thiosemicarbazone Drug Info [526354]
5-Chloro-1-(4-chloro-benzyl)-1H-indole-2,3-dione Drug Info [526832]
Benzoyl-Arginine-Alanine-Methyl Ketone Drug Info [551393]
GNF-PF-4478 Drug Info [530968]
K-777 Drug Info [530398]
L-755507 Drug Info [530512]
MANIDIPINE Drug Info [530877]
N1,N4-bis(5-chloro-2-methylphenyl)succinamide Drug Info [530512]
TRICLABENDAZOLE Drug Info [530877]
VITAMIN K2 Drug Info [530877]
WRR-112 Drug Info [551393]
WRR-204 Drug Info [551393]
WRR-99 Drug Info [551393]
Binder Vinylsulphones Drug Info [536135]
References
Ref 521680ClinicalTrials.gov (NCT00157586) Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND). U.S. National Institutes of Health.
Ref 540554(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: 3931).
Ref 546489Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008526)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 526354J Med Chem. 2002 Jun 20;45(13):2695-707.Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain.
Ref 526832Bioorg Med Chem Lett. 2003 Oct 20;13(20):3527-30.Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain.
Ref 528258Bioorg Med Chem Lett. 2006 Aug 15;16(16):4405-9. Epub 2006 Jun 15.Design, synthesis, and biochemical evaluation of novel cruzain inhibitors with potential application in the treatment of Chagas' disease.
Ref 530281J Med Chem. 2009 Aug 27;52(16):5005-8.Divergent modes of enzyme inhibition in a homologous structure-activity series.
Ref 530398Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21. Epub 2009 Sep 3.Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.
Ref 530512J Med Chem. 2010 Jan 14;53(1):37-51.Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease.
Ref 530877J Med Chem. 2010 May 27;53(10):4259-65.Colloid formation by drugs in simulated intestinal fluid.
Ref 530968J Med Chem. 2010 Jul 8;53(13):4891-905.Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.
Ref 531227Bioorg Med Chem. 2010 Nov 15;18(22):7826-35. Epub 2010 Sep 29.Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents.
Ref 536135Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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