K777

K777 is a cysteine protease inhibitor. It inhibits human cathepsin S (Ki = 0.002 µM) and human cathepsin L (Ki = 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 (Kis = 0.4, 3, >100 µM, respectively), as well as the SARS-CoV-2 cysteine proteases papain-like protease (PLpro) and main protease (Mpro), also known as the 3C-like protease (3CLpro, Kis = >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 = 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. 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.Formal Name: 4-methyl-N-[(1S)-2-oxo-2-[[(1S)-1-(2-phenylethyl)-3-(phenylsulfonyl)-2-propen-1-yl]amino]-1-(phenylmethyl)ethyl]-1-piperazinecarboxamide. CAS Number: 233277-99-1. Synonyms: APC-3316, CRA-3316, K11777, MePip-Phe-hPhe-VSphi. Molecular Formula: C32H38N4O4S. Formula Weight: 574.7. Purity: >98% (mixture of isomers). Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. SMILES: O=S(C1=CC=CC=C1)(/C=C/[C@H](CCC2=CC=CC=C2)NC([C@H](CC3=CC=CC=C3)NC(N4CCN(C)CC4)=O)=O)=O. InChi Code: InChI=1S/C32H38N4O4S/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/h2-16,19,24,28,30H,17-18,20-23,25H2,1H3,(H,33,37)(H,34,38)/b24-19+/t28-,30-/m0/s1. InChi Key: RHJLQMVZXQKJKB-FPHSVDBKSA-N.