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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2D Structure
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Physico-chemical Properties
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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
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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
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]