K777 [K11777]

Specifications / Handling

More Information
Product Details
Synonyms	K-777; K-11777; N-Pip-F-hF-VS Phenyl; N-Pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl; N-Methyl-piperazinyl-L-phenylalanyl-L-homophenylalanyl-vinyl sulfone
Product Type	Chemical
Properties
Formula	C₃₂H₃₈N₄O₄S
MW	574.7
CAS	233277-99-1
Purity Chemicals	≥98% (NMR)
Appearance	Solid.
Solubility	Soluble in DMSO. Insoluble in water.
Identity	Determined by ¹H-NMR.
Other Product Data	Contains ~10% other isomer product.
InChi Key	RHJLQMVZXQKJKB-FPHSVDBKSA-N
Smiles	CN1CCN(C(N[C@@](C(N[C@@](/C=C/S(C2=CC=CC=C2)(=O)=O)([H])CCC3=CC=CC=C3)=O)([H])CC4=CC=CC=C4)=O)CC1
Shipping and Handling
Shipping	AMBIENT
Short Term Storage	+4°C
Long Term Storage	-20°C
Handling Advice	Keep cool and dry.
Use/Stability	Stable for at least 2 years after receipt when stored at -20°C.
Documents
MSDS	Download PDF
Product Specification Sheet
Datasheet	Download PDF

Product-specific References

Description

Broad-range cathepsin inhibitor (for all known cathepsins) useful for inflammasome inhibition. Inhibits cathepsins B, L, S, C, V, K and papain in cell-free assays. Inhibits cathepsin X as well.
Suppresses particle-induced NLRP3 activation and IL-1beta secretion more efficiently than Ca074Me (cathepsin B inhibitor), which in contrast suppresses nigericin-induced IL-1beta secretion.
Selectively inhibits particle-induced cell death but not nigericin- or sAdT-induced cell death.
Potent and selective CCR4 antagonist.
Potent, irreversible cysteine protease inhibitor.
Potent cysteine protease cruzain (cruzipain) inhibitor. Active against Trypanosoma cruzi the causative agent of Chagas' disease, a parasitic infection which is a leading cause of heart disease.
Antiparasitic agent with anti-trypanosomal , anti-leishmanial, anti-schistosomiasis, anti-amebiasis (EhCP1 (E. Histolytica cysteine proteinase 1)), anti-anthelmintic (hookworm first-stage larvae) and anti-cryptosporidial activity.
Shown to have antiviral activity by targeting cathepsin-mediated cell entry.

Product References

Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection: J. Engel, et al.; J. Exp. Med. 188, 725 (1998)
In vitro evaluation of the disposition of A novel cysteine protease inhibitor: W. Jacobsen, et al.; Drug Metab. Dispos. 28, 1343 (2000)
Leishmania tropica: cysteine proteases are essential for growth and pathogenicity: H. Mahmoudzadeh-Niknam, et al.; Exp. Parasitol. 106, 158 (2004)
A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi: S.C. Barr, et al.; Antimicrob. Agents Chemother. 49, 5160 (2005)
Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model: S.G. Melendez-Lopez, et al.; Eukaryot. Cell 6, 1130 (2007)
Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor: M.H. Abdulla, et al.; PLoS Med. 4, e14 (2007)
Vinyl sulfones as antiparasitic agents and a structural basis for drug design: I.D. Kerr, et al.; J. Biol. Chem. 284, 25697 (2009)
In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi: Y.T. Chen, et al.; PLoS Negl. Trop. Dis. 4, e825 (2010)
Cure of hookworm infection with a cysteine protease inhibitor: J.J. Vermeire, et al.; PLoS Negl. Trop. Dis. 6, e1680 (2012)
Mapping inhibitor binding modes on an active cysteine protease via NMR spectroscopy: G.M. Lee, et al.; Biochem. 51, 10087 (2012)
Active cathepsins B, L, and S in murine and human pancreatitis: V. Lyo, et al.; Am. J. Physiol. Gastrointest. Liver Physiol. 303, G894 (2012)
Internalization of CCR4 and inhibition of chemotaxis by K777, a potent and selective CCR4 antagonist: T. Sato, et al.; Pharmacology 91, 305 (2013)
A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection: M. Ndao, et al.; Antimicrob. Agents Chemother. 57, 6063 (2013)
Reversible cysteine protease inhibitors show promise for a Chagas Disease cure: M. Ndao, et al.; Antimicrob. Agents Chemother. 58, 1167 (2014)
Protease inhibitors targeting coronavirus and filovirus entry: Y. Zhou, et al.; Antiviral Res. 116, 76 (2015)
Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1beta activation: G.M. Orlowski, et al.; J. Leukoc. Biol. 102, 7 (2017)

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