K777 (K11777) CAS No. 233277-99-1

Product Description

K777 (K11777) is an orally active, irreversible vinyl-sulfone–based di-peptide analog that acts simultaneously as a potent cysteine protease inhibitor, a CYP3A4 blocker (IC50 60 nM) and a selective CCR4 antagonist that suppresses CCL17-driven chemotaxis (IC50 8.9 nM) and induces ~50 % CCR4 internalization. By covalently targeting host cathepsins B and L, K777 irreversibly inactivates key enzymes essential for pathogen entry, thereby blocking the replication of Trypanosoma cruzi (via inhibition of cruzain) and providing broad-spectrum antiviral protection against coronaviruses (SARS-CoV, SARS-CoV-2, HCoV-229E, NL63, MERS-CoV), filoviruses (EBOV, SUDV, TAFV, RESTV, BEBOV, MARV) and Nipah virus with single-digit-nanomolar IC50 values (0.42–46 nM). In pre-clinical models, K777 rescues C57BL/6 IFN-γR-KO mice from lethal Cryptosporidium parvum infection when dosed orally at 35–105 mg/kg twice daily for 10 days, and it synergizes with the TMPRSS2 inhibitor Camostat to achieve ~90 % suppression of viral entry in TMPRSS2-expressing Caco-2 intestinal cells. Notably, K777 retains sub-100 nM antiviral potency in SARS-CoV-2-infected Vero E6 and HeLa/ACE2 cells without cytotoxicity up to 100 µM, underscoring its translational potential as a host-targeted therapeutic against a wide array of infectious diseases.

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Product Use & Characteristics

1. Identity & Physicochemical Data

   Synonyms: K11777

   Molecular Formula: C₃₂H₃₈N₄O₄S

   Molecular Weight: 574.7 g mol⁻¹

   IUPAC Name: N-[(2S)-1-[[(E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]-4-methylpiperazine-1-carboxamide

   Core Structure: di-peptide vinyl-sulfone warhead (irreversible electrophile)

2. Mechanism of Action & Pharmacological Characteristics

   Primary Target(s): Host cysteine proteases cathepsin B & cathepsin L; parasite enzyme cruzain (Trypanosoma cruzi)

   Secondary Targets: CYP3A4 (IC₅₀ 60 nM); CCR4 chemokine receptor (antagonist & internalization inducer; IC₅₀ 8.9 nM for chemotaxis, 57 nM for ligand binding)

   Mode of Inhibition: irreversible covalent Michael addition of the active-site cysteine to the vinyl-sulfone; reaction ΔG ≈ –26.7 kcal mol⁻¹ (QM/MM)

   Pharmacodynamics: blocks pathogen entry by preventing cathepsin-mediated cleavage of viral/filoviral spike proteins; suppresses Th2-lymphocyte chemotaxis via CCR4 internalization (~50 % surface loss)

3. Antiviral & Antiparasitic Potency (representative IC₅₀ / EC₅₀)

   Coronaviruses: SARS-CoV 0.68 nM, SARS-CoV-2 (Vero E6) 74 nM, (HeLa/ACE2) 4 nM, HCoV-229E 1.48 nM, NL63 6.78 nM, MERS-CoV 46 nM

   Filoviruses: EBOV 0.87 nM, SUDV 1.14 nM, MARV 1.9 nM, etc.

   Nipah virus: 0.42 nM

   Trypanosoma cruzi (cruzain): irreversible inhibition demonstrated; active in vivo against lethal Chagas models

   Cryptosporidium parvum: orally rescues IFN-γR-KO mice (35–105 mg kg⁻¹ b.i.d. × 10 d)

4. In Vitro & In Vivo Features

   Administration Route: oral, well absorbed

   Cellular Safety: no cytotoxicity up to 100 µM in Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, Calu-3 cells

   Combination Benefit: additive to synergistic blockade (~90 %) with TMPRSS2 inhibitor Camostat in TMPRSS2-positive Caco-2 cells

   Selectivity: inactive against alphavirus (CHIKV), rhabdovirus (VSV), flavivirus (HCV), retroviruses MLV-A/XMRV, arenaviruses (LASV, JUNV) at 100 nM

5. Uses / Application Areas

   Broad-spectrum antiviral therapeutic candidate (coronaviruses, filoviruses, paramyxoviruses)

   Antiparasitic agent for Chagas disease (via cruzain inhibition)

   Anti-cryptosporidiosis agent in immunocompromised hosts

   Experimental tool to dissect cathepsin-dependent viral entry pathways

   Potential anti-allergic/immunomodulatory agent via CCR4 antagonism

Why us!

Qingdao Sigma Chemical Co., Ltd., established in January 2017 and headquartered in Qingdao, China, is a reliable chemical supplier. Specializing in pharmaceuticals, biochemical intermediates, and research chemicals, the company offers a diverse product portfolio, including peptides (e.g., Tirzepatide, Semaglutide), nootropics, veterinary products, and APIs, often marketed with ≥99% purity and COA certification. We provides R&D, custom synthesis, and contract manufacturing services at various scales, while claiming a global export presence across 100+ countries. With international warehouses in the USA, Europe, Australia, and Canada, Qingdao Sigma Chemical also facilitates drop-shipping and reshipments, positioning itself as a key supplier for laboratory and research applications.