K777

K777 is a cysteine protease inhibitor.¹ It inhibits human cathepsin S (K_i = 0.002 µM) and human cathepsin L (K_i = 0.05 µM), which cleaves the severe acute respiratory coronavirus 2 (SARS-CoV-2) spike glycoprotein, also known as the surface glycoprotein. K777 is selective for these proteases over human cathepsin K, -B, and -C (K_is = 0.4, 3, >100 µM, respectively), as well as the SARS-CoV-2 cysteine proteases papain-like protease (PL^pro) and main protease (M^pro), also known as the 3C-like protease (3CL^pro; K_is = >100 µM for both). It prevents cleavage of the spike protein S1 subunit in vitro and reduces the cytopathic effect of SARS-CoV-2 in infected Vero E6, HeLa/ACE2, and A549/ACE2 cells (EC₅₀s = <0.074, 0.004, and <0.080 µM, respectively). K777 induces mortality in T. b. brucei trypanosomes (IC₅₀ = 0.1 µM) and reduces myocardial damage in a canine model of T. cruzi infection when administered at a dose of 50 mg/kg twice per day.^2,3 It also inhibits chemokine (C-C motif) ligand 17 (CCL17) binding to, and CCL17-induced chemotaxis of, HuT 78 cells (IC₅₀s = 0.057 and 0.0089 µM, respectively), as well as induces chemokine (C-C motif) receptor 4 (CCR4) internalization.⁴

WARNING This product is not for human or veterinary use.

1. Mellott, D.M., Tseng, C.-T., Drelich, A., et al. A clinical-stage cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells. ACS Chem. Biol. 16(4), 642-650 (2021).

2. Troeberg, L., Morty, R.E., Pike, R.N., et al. Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei. Exp. Parasitol. 91(4), 349-355 (1999).

3. Barr, S.C., Warner, K.L., Kornreic, B.G., et al. A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob. Agents Chemother. 49(12), 5160-5161 (2005).

4. Sato, T., Iwase, M., Miyama, M., et al. Internalization of CCR4 and inhibition of chemotaxis by K777, a potent and selective CCR4 antagonist. Pharmacology 91(5-6), 305-313 (2013).