| Description | K777 is a potent, orally active and irreversible inhibitor of cysteine protease. K777 is a potent CYP3A4 inhibitor (IC50= 60 nM). K777 is also a selective CCR4 antagonist featuring the potent chemotaxis inhibition. K777 irreversibly inhibits Cruzain, which is the major cysteine protease of Trypansoma cruzi, and cathepsins B and L. K777 targets cathepsin-mediated cell entry and wxibits a broad-spectrum antiviral activity. K777 inhibits EBOV and SARS-CoV pseudovirus entry with IC50 values of 0.87 nM and 0.68 nM, respectively. |
| In vitro | K777 is a broad-spectrum antiviral and inhibits SARS-CoV, HCoV-229E, NL63, MERS-CoV, EBOV, SUDV, TAFV, RESTV, BEBOV, MARV and Nipah pseudovirus entry with IC50 values of 0.68 nM, 1.48 nM, 6.78 nM, 46.12 nM, 0.87 nM, 1.14 nM, 2.26 nM, 3.37 nM, 5.91 nM, 1.9 nM and 0.42 nM, respectively. K777 alone demonstrates up to 70% inhibition of 229E-S-mediated transduction in TMPRSS2 expressing cells. Simultaneous treatment with Camostat and K777 increases inhibition to ~ 90%[1]. K777 inhibits both CCL17 binding and CCL17-induced chemotaxis in Hut78 cells with IC50s of 57 and 8.9 nM, respectively. The K777-mediated inhibition of chemotaxis is potent even in the presence of a 10-fold higher concentration of CCL17. K777 induces CCR4 internalization with a 50% reduction of cell surface CCR4[3]. |
| In vivo | In C57BL/6 IFN-γR-KO mice, K777 ( 35-105 mg/kg; p.o.) rescues mice from otherwise lethal infections[4]. |
| Target activity | CYP3A4:60 nM (IC50) |
| Synonyms | APC-3316 |
| molecular weight | 574.73 |
| Molecular formula | C32H38N4O4S |
| CAS | 233277-99-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 90 mg/mL (156.6 mM), Sonication is recommended. |
| References | 1. Zhou Y, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015 Apr;116:76-84. 2. Jacobsen W, et al. In vitro evaluation of the disposition of A novel cysteine protease inhibitor. Drug Metab Dispos. 2000 Nov;28(11):1343-51. 3. Sato T, et al. Internalization of CCR4 and inhibition of chemotaxis by K777, a potent and selective CCR4 antagonist. Pharmacology. 2013;91(5-6):305-13. 4. Ndao M, et al. A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection. Antimicrob Agents Chemother. 2013 Dec;57(12):6063-73. |