Target Information
Target General Information | Top | |||||
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Target ID |
T30372
(Former ID: TTDR00982)
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Target Name |
Trypanosoma Cruzipain (Trypano CYSP)
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Synonyms |
Cruzaine; Major cysteine proteinase
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Gene Name |
Trypano CYSP
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Parasitic worm infestation [ICD-11: 1F90] | |||||
Function |
The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 3.4.22.51
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Sequence |
MSGWARALLLAAVLVVMACLVPAATASLHAEETLTSQFAEFKQKHGRVYESAAEEAFRLS
VFRENLFLARLHAAANPHATFGVTPFSDLTREEFRSRYHNGAAHFAAAQERARVPVKVEV VGAPAAVDWRARGAVTAVKDQGQCGSCWAFSAIGNVECQWFLAGHPLTNLSEQMLVSCDK TDSGCSGGLMNNAFEWIVQENNGAVYTEDSYPYASGEGISPPCTTSGHTVGATITGHVEL PQDEAQIAAWLAVNGPVAVAVDASSWMTYTGGVMTSCVSEQLDHGVLLVGYNDSAAVPYW IIKNSWTTQWGEEGYIRIAKGSNQCLVKEEASSAVVGGPGPTPEPTTTTTTSAPGPSPSY FVQMSCTDAACIVGCENVTLPTGQCLLTTSGVSAIVTCGAETLTEEVFLTSTHCSGPSVR SSVPLNKCNRLLRGSVEFFCGSSSSGRLADVDRQRRHQPYHSRHRRL Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | TRICLABENDAZOLE | Drug Info | Approved | Helminth infection | [2] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 29 Inhibitor drugs | + | ||||
1 | TRICLABENDAZOLE | Drug Info | [1] | |||
2 | MANIDIPINE | Drug Info | [1] | |||
3 | L-755507 | Drug Info | [3] | |||
4 | (3Z)-1H-indole-2,3-dione 3-thiosemicarbazone | Drug Info | [4] | |||
5 | 1-(1-(3-nitrophenyl)propylidene)thiosemicarbazide | Drug Info | [5] | |||
6 | 1-(3,4-dihydronaphthalen-1-yl)ethanone | Drug Info | [5] | |||
7 | 1-(3-Methoxy-benzyl)-5-methyl-1H-indole-2,3-dione | Drug Info | [4] | |||
8 | 1-(bis(3-bromophenyl)methylene)thiosemicarbazide | Drug Info | [5] | |||
9 | 2-(cycloheptylamino)-2-oxoethyl 2-aminonicotinate | Drug Info | [6] | |||
10 | 2-(trifluoromethyl)benzaldehyde thiosemicarbazone | Drug Info | [7] | |||
11 | 2-methoxy-1-naphthaldehyde thiosemicarbazone | Drug Info | [7] | |||
12 | 3',4'-dichloroacetophenonethiosemicarbazone | Drug Info | [8] | |||
13 | 3'-bromopropiophenonethiosemicarbazone | Drug Info | [8] | |||
14 | 3,4-dichlorobenzaldehyde thiosemicarbazone | Drug Info | [7] | |||
15 | 3,5-dichlorobenzaldehyde thiosemicarbazone | Drug Info | [7] | |||
16 | 3-(trifluoromethyl)benzaldehyde thiosemicarbazone | Drug Info | [7] | |||
17 | 3-amino-5-(furan-2-yl)biphenyl-2,4-dicarbonitrile | Drug Info | [3] | |||
18 | 3-chloro-N-(4-(phenyldiazenyl)phenyl)benzamide | Drug Info | [3] | |||
19 | 5-(3,4-dichlorophenyl)-1H-pyrazol-3-ol | Drug Info | [3] | |||
20 | 5-(4-bromophenyl)-2-furaldehyde thiosemicarbazone | Drug Info | [7] | |||
21 | 5-Chloro-1-(4-chloro-benzyl)-1H-indole-2,3-dione | Drug Info | [4] | |||
22 | Benzoyl-Arginine-Alanine-Methyl Ketone | Drug Info | [9] | |||
23 | GNF-PF-4478 | Drug Info | [10] | |||
24 | K-777 | Drug Info | [11] | |||
25 | N1,N4-bis(5-chloro-2-methylphenyl)succinamide | Drug Info | [3] | |||
26 | VITAMIN K2 | Drug Info | [1] | |||
27 | WRR-112 | Drug Info | [9] | |||
28 | WRR-204 | Drug Info | [9] | |||
29 | WRR-99 | Drug Info | [9] | |||
Binder | [+] 1 Binder drugs | + | ||||
1 | Vinylsulphones | Drug Info | [12] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: WRR-112 | Ligand Info | |||||
Structure Description | THE CYSTEINE PROTEASE CRUZAIN BOUND TO WRR-112 | PDB:1EWM | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [13] |
PDB Sequence |
APAAVDWRAR
10 GAVTAVKDQG20 QCGSCWAFSA30 IGNVECQWFL40 AGHPLTNLSE50 QMLVSCDKTD 60 SGCSGGLMNN70 AFEWIVQENN78B GAVYTEDSYP87 YASGEGISPP94 CTTSGHTVGA 105 TITGHVELPQ115 DEAQIAAWLA125 VNGPVAVAVD135 ASSWMTYTGG147 VMTSCVSEQL 157 DHGVLLVGYN167 DSAAVPYWII173 KNSWTTQWGE183 EGYIRIAKGS193 NQCLVKEEAS 207 SAVVG
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Ligand Name: WRR-99 | Ligand Info | |||||
Structure Description | CRYSTAL STRUCTURE OF CRUZAIN BOUND TO WRR-99 | PDB:1EWL | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [14] |
PDB Sequence |
APAAVDWRAR
10 GAVTAVKDQG20 QCGSCWAFSA30 IGNVECQWFL40 AGHPLTNLSE50 QMLVSCDKTD 60 SGCSGGLMNN70 AFEWIVQENN78B GAVYTEDSYP87 YASGEGISPP94 CTTSGHTVGA 105 TITGHVELPQ115 DEAQIAAWLA125 VNGPVAVAVD135 ASSWMTYTGG147 VMTSCVSEQL 157 DHGVLLVGYN167 DSAAVPYWII173 KNSWTTQWGE183 EGYIRIAKGS193 NQCLVKEEAS 207 SAVVG
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Colloid formation by drugs in simulated intestinal fluid. J Med Chem. 2010 May 27;53(10):4259-65. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 3 | 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. | |||||
REF 4 | 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. | |||||
REF 5 | 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. | |||||
REF 6 | Divergent modes of enzyme inhibition in a homologous structure-activity series. J Med Chem. 2009 Aug 27;52(16):5005-8. | |||||
REF 7 | 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. | |||||
REF 8 | Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorg Med Chem. 2010 Nov 15;18(22):7826-35. | |||||
REF 9 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 10 | Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem. 2010 Jul 8;53(13):4891-905. | |||||
REF 11 | 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. | |||||
REF 12 | Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40. | |||||
REF 13 | THE CYSTEINE PROTEASE CRUZAIN BOUND TO WRR-112 | |||||
REF 14 | CRYSTAL STRUCTURE OF CRUZAIN BOUND TO WRR-99 |
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