K-11777

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206491

CAS#: 233277-99-1

Description: K-11777, also known as APC 3316; and K 777, is a a potent, irreversible cysteine protease inhibitor and a potent and selective CCR4 antagonist. Its therapeutic targets are cruzain, a cysteine protease of the protozoan parasite Trypanosoma cruzi, and cathepsins B and L, which are associated with cancer progression. K777 inhibited both CCL17 binding and CCL17-induced chemotaxis in Hut78 cells (IC50: 57 and 8.9 nmol/l, respectively). K777 induced CCR4 internalization, with a ∼50% reduction of cell surface CCR4. K777 did not inhibit CXCR4-induced chemotaxis or internalization and did not bring about Ca(2+) mobilization by itself.


Price and Availability

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1g
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Size
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2g
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Size
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5g
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K-11777 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206491
Name: K-11777
CAS#: 233277-99-1
Chemical Formula: C32H38N4O4S
Exact Mass: 574.2614
Molecular Weight: 574.74
Elemental Analysis: C, 66.87; H, 6.66; N, 9.75; O, 11.13; S, 5.58


Synonym: APC-3316; APC3316; APC 3316; K-11777; K 11777; K11777; K 777; K-777; K777; CRA-3316; CRA3316; CRA 3316.

IUPAC/Chemical Name: 4-methyl-N-((S)-1-oxo-3-phenyl-1-(((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino)propan-2-yl)piperazine-1-carboxamide

InChi Key: RHJLQMVZXQKJKB-FPHSVDBKSA-N

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

SMILES Code: O=C(N1CCN(C)CC1)N[C@@H](CC2=CC=CC=C2)C(N[C@@H](CCC3=CC=CC=C3)/C=C/S(=O)(C4=CC=CC=C4)=O)=O


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, Barnard D, Pöhlmann S, McKerrow JH, Renslo AR, Simmons G. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015 Apr;116:76-84. doi: 10.1016/j.antiviral.2015.01.011. Epub 2015 Feb 7. PubMed PMID: 25666761.

2: Steverding D. Evaluation of trypanocidal activity of combinations of anti-sleeping sickness drugs with cysteine protease inhibitors. Exp Parasitol. 2015 Apr-May;151-152:28-33. doi: 10.1016/j.exppara.2015.01.016. Epub 2015 Feb 4.
PubMed PMID: 25662707.

3: Rhee SW, Bradford WW, Malerich JP, Tanga MJ. Carbon-14 labeling of K777•HCl, a therapeutic agent for Chagas disease. J Labelled Comp Radiopharm. 2013 Jul-Aug;56(9-10):461-3. doi: 10.1002/jlcr.3107. Epub 2013 Aug 19. PubMed PMID: 24285521.

4: Ndao M, Nath-Chowdhury M, Sajid M, Marcus V, Mashiyama ST, Sakanari J, Chow E, Mackey Z, Land KM, Jacobson MP, Kalyanaraman C, McKerrow JH, Arrowood MJ, Caffrey CR. A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection. Antimicrob Agents Chemother. 2013 Dec;57(12):6063-73. doi: 10.1128/AAC.00734-13. Epub 2013 Sep 23. PubMed PMID: 24060869; PubMed Central PMCID: PMC3837922.

5: Sato T, Iwase M, Miyama M, Komai M, Ohshima E, Asai A, Yano H, Miki I. Internalization of CCR4 and inhibition of chemotaxis by K777, a potent and selective CCR4 antagonist. Pharmacology. 2013;91(5-6):305-13. doi: 10.1159/000350390. Epub 2013 Jun 5. PubMed PMID: 23751403.

6: Lee GM, Balouch E, Goetz DH, Lazic A, McKerrow JH, Craik CS. Mapping inhibitor binding modes on an active cysteine protease via nuclear magnetic resonance spectroscopy. Biochemistry. 2012 Dec 18;51(50):10087-98. doi: 10.1021/bi301305k.
Epub 2012 Dec 10. PubMed PMID: 23181936; PubMed Central PMCID: PMC3566641.

7: Lyo V, Cattaruzza F, Kim TN, Walker AW, Paulick M, Cox D, Cloyd J, Buxbaum J,
Ostroff J, Bogyo M, Grady EF, Bunnett NW, Kirkwood KS. Active cathepsins B, L, and S in murine and human pancreatitis. Am J Physiol Gastrointest Liver Physiol.
2012 Oct 15;303(8):G894-903. doi: 10.1152/ajpgi.00073.2012. Epub 2012 Aug 16. PubMed PMID: 22899821; PubMed Central PMCID: PMC3469694.

8: Vermeire JJ, Lantz LD, Caffrey CR. Cure of hookworm infection with a cysteine
protease inhibitor. PLoS Negl Trop Dis. 2012;6(7):e1680. doi: 10.1371/journal.pntd.0001680. Epub 2012 Jul 3. PubMed PMID: 22802972; PubMed Central PMCID: PMC3389033.

9: Nicoll-Griffith DA. Use of cysteine-reactive small molecules in drug discovery for trypanosomal disease. Expert Opin Drug Discov. 2012 Apr;7(4):353-66. doi: 10.1517/17460441.2012.668520. Epub 2012 Mar 6. Review. PubMed PMID: 22458506.

10: Yang PY, Wang M, He CY, Yao SQ. Proteomic profiling and potential cellular target identification of K11777, a clinical cysteine protease inhibitor, in Trypanosoma brucei. Chem Commun (Camb). 2012 Jan 21;48(6):835-7. doi: 10.1039/c1cc16178d. Epub 2011 Nov 28. PubMed PMID: 22124229.

11: Cobo ER, Reed SL, Corbeil LB. Effect of vinyl sulfone inhibitors of cysteine
proteinases on Tritrichomonas foetus infection. Int J Antimicrob Agents. 2012 Mar;39(3):259-62. doi: 10.1016/j.ijantimicag.2011.09.026. Epub 2011 Nov 21. PubMed PMID: 22104282; PubMed Central PMCID: PMC3279618.

12: Doyle PS, Zhou YM, Hsieh I, Greenbaum DC, McKerrow JH, Engel JC. The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog. 2011 Sep;7(9):e1002139. doi: 10.1371/journal.ppat.1002139. Epub 2011 Sep 1. PubMed PMID: 21909255; PubMed Central PMCID: PMC3164631.

13: Jílková A, Rezácová P, Lepsík M, Horn M, Váchová J, Fanfrlík J, Brynda J, McKerrow JH, Caffrey CR, Mares M. Structural basis for inhibition of cathepsin B
drug target from the human blood fluke, Schistosoma mansoni. J Biol Chem. 2011 Oct 14;286(41):35770-81. doi: 10.1074/jbc.M111.271304. Epub 2011 Aug 10. PubMed PMID: 21832058; PubMed Central PMCID: PMC3195637.

14: Sajid M, Robertson SA, Brinen LS, McKerrow JH. Cruzain : the path from target validation to the clinic. Adv Exp Med Biol. 2011;712:100-15. doi: 10.1007/978-1-4419-8414-2_7. Review. PubMed PMID: 21660661.

15: Chen YT, Brinen LS, Kerr ID, Hansell E, Doyle PS, McKerrow JH, Roush WR. In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi. PLoS Negl Trop Dis. 2010 Sep 14;4(9). pii: e825. doi: 10.1371/journal.pntd.0000825. PubMed PMID: 20856868; PubMed Central PMCID: PMC2939063.

16: McKerrow JH, Doyle PS, Engel JC, Podust LM, Robertson SA, Ferreira R, Saxton
T, Arkin M, Kerr ID, Brinen LS, Craik CS. Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:263-9. PubMed PMID: 19753483; PubMed Central PMCID: PMC4156466.

17: Chen YT, Lira R, Hansell E, McKerrow JH, Roush WR. Synthesis of macrocyclic trypanosomal cysteine protease inhibitors. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5860-3. doi: 10.1016/j.bmcl.2008.06.012. Epub 2008 Jun 10. PubMed PMID: 18585034; PubMed Central PMCID: PMC2642929.

18: Kongkerd N, Uparanukraw P, Morakote N, Sajid M, McKerrow JH. Identification and characterization of a cathepsin L-like cysteine protease from Gnathostoma spinigerum. Mol Biochem Parasitol. 2008 Aug;160(2):129-37. doi: 10.1016/j.molbiopara.2008.05.001. Epub 2008 May 8. PubMed PMID: 18554733.

19: Meléndez-López SG, Herdman S, Hirata K, Choi MH, Choe Y, Craik C, Caffrey CR, Hansell E, Chávez-Munguía B, Chen YT, Roush WR, McKerrow J, Eckmann L, Guo J, Stanley SL Jr, Reed SL. Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model. Eukaryot Cell. 2007 Jul;6(7):1130-6. Epub 2007 May 18. PubMed PMID: 17513563; PubMed Central PMCID: PMC1951106.

20: Abdulla MH, Lim KC, Sajid M, McKerrow JH, Caffrey CR. Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor. PLoS Med. 2007 Jan;4(1):e14. PubMed PMID: 17214506; PubMed Central PMCID: PMC1764436.