K777   Click here for help

GtoPdb Ligand ID: 11515

Synonyms: K-777 | K11777 | S-001 | SLV213
PDB Ligand
Compound class: Synthetic organic
Comment: K777 is a clinical stage irreversible cysteine protease inhibitor. It has reported activity at human cathepsin L and other CA clade cysteine proteases [2-5]. Original reports revealed anti-parasitic effects in vitro and in animal models [1-2,6].

SARS-CoV-2: Cathepsin L in human host cells is implicated in the processing (cleavage) of the viral spike protein of SARS coronaviruses, that is part of the viral entry process. K777 blocks SARS-CoV-2 infection in vitro.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 15
Topological polar surface area 107.2
Molecular weight 576.28
XLogP 4.17
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CN1CCN(CC1)C(=O)N[C@H](C(=O)N[C@H](CCS(=O)(=O)c1ccccc1)CCc1ccccc1)Cc1ccccc1
Isomeric SMILES CN1CCN(CC1)C(=O)N[C@H](C(=O)N[C@H](CCS(=O)(=O)c1ccccc1)CCc1ccccc1)Cc1ccccc1
InChI InChI=1S/C32H40N4O4S/c1-35-20-22-36(23-21-35)32(38)34-30(25-27-13-7-3-8-14-27)31(37)33-28(18-17-26-11-5-2-6-12-26)19-24-41(39,40)29-15-9-4-10-16-29/h2-16,28,30H,17-25H2,1H3,(H,33,37)(H,34,38)/t28-,30-/m0/s1
InChI Key VZSXPUDQSLKVIR-JDXGNMNLSA-N
References
1. Doyle PS, Zhou YM, Engel JC, McKerrow JH. (2007)
A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection.
Antimicrob Agents Chemother, 51 (11): 3932-9. [PMID:17698625]
2. Engel JC, Doyle PS, Hsieh I, McKerrow JH. (1998)
Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection.
J Exp Med, 188 (4): 725-34. [PMID:9705954]
3. Mellott DM, Tseng CT, Drelich A, Fajtová P, Chenna BC, Kostomiris DH, Hsu J, Zhu J, Taylor ZW, Kocurek KI et al.. (2021)
A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells.
ACS Chem Biol, 16 (4): 642-650. [PMID:33787221]
4. Palmer JT, Rasnick D, Klaus JL, Brömme D. (1995)
Vinyl sulfones as mechanism-based cysteine protease inhibitors.
J Med Chem, 38 (17): 3193-6. [PMID:7650671]
5. Somoza JR, Zhan H, Bowman KK, Yu L, Mortara KD, Palmer JT, Clark JM, McGrath ME. (2000)
Crystal structure of human cathepsin V.
Biochemistry, 39 (41): 12543-51. [PMID:11027133]
6. Yang PY, Wang M, He CY, Yao SQ. (2012)
Proteomic profiling and potential cellular target identification of K11777, a clinical cysteine protease inhibitor, in Trypanosoma brucei.
Chem Commun (Camb), 48 (6): 835-7. [PMID:22124229]