MK-886

• CAT Number: I000650
• CAS Number: 118414-82-7
• Molecular Formula: C27H34ClNO2S
• Molecular Weight: 472.1
• Purity: ≥95%
• Target: 5-Lipoxygenase
• Solubility: DMSO ≥ 32 mg/mL
• Storage: Store at RT
• IC50: 2.5 nM ( leukotriene ,LT )
• InChI: InChI=1S/C27H34ClNO2S/c1-6-7-14-32-25-22-15-20(18(2)3)10-13-23(22)29(17-19-8-11-21(28)12-9-19)24(25)16-27(4,5)26(30)31/h8-13,15,18H,6-7,14,16-17H2,1-5H3,(H,30,31)
• InChIKey: QAOAOVKBIIKRNL-UHFFFAOYSA-N
• SMILES: OC(C(C)(C)CC1=C(SC(C)(C)C)C(C=C(C(C)C)C=C2)=C2N1CC3=CC=C(Cl)C=C3)=O

MK886 is a potent 5-lipoxygenase activating protein inhibitor (FLAP) also a non-competitive inhibitor of PPAR alpha. a potent inhibitor of leukotriene (LT) biosynthesis in intact human polymorphonuclear leukocytes with IC 50 of 2.5 nM. Block the synthessis of leukotrien intact activate leukocyte.

In vitro: MK886 inhibit PPAR alpha by a non-competitive mechanism as shown by its effects on the binding of arachidonic acid to PPAR alpha protein. The expression of keratin-1 is reduced by MK886 in a culture of mouse primary keratinocytes. MK886 functioning as a non-competitive inhibitor of PPAR alpha, but may also indicate that PPAR alpha is not directly involved in MK886-induced apoptosis.
In vivo: L-663,536 inhibit A23187-induced LTB4 formation by rat peripheral blood and elicited PMN. The compound inhibited leukotriene biosynthesis in vivo in a rat pleurisy model (ED50, 0.2 mg/kg p.o.), an inflamed rat paw model (ED50, 0.8 mg/kg)

Reference

1:Potentiation of hypericin-mediated photodynamic therapy cytotoxicity by MK-886: focus on ABC transporters, GDF-15 and redox status. Kuchárová B, Mikeš J, Jendželovský R, Vargová J, Mikešová L, Jendželovská Z, Kovaľ J, Fedoročko P.Photodiagnosis Photodyn Ther. 2015 Sep;12(3):490-503. doi: 10.1016/j.pdpdt.2015.04.008. Epub 2015 May 21. PMID: 26003114 2:Effect of MK-886 on Ca2+ level and viability in PC3 human prostate cancer cells. Huang JK, Huang CC, Lu T, Chang HT, Lin KL, Tsai JY, Liao WC, Chien JM, Jan CR.Basic Clin Pharmacol Toxicol. 2009 Jun;104(6):441-7. doi: 10.1111/j.1742-7843.2009.00413.x. Epub 2009 Apr 3. PMID: 19371256 Free Article3:MK-886, an inhibitor of the 5-lipoxygenase-activating protein, inhibits cyclooxygenase-1 activity and suppresses platelet aggregation. Koeberle A, Siemoneit U, Northoff H, Hofmann B, Schneider G, Werz O.Eur J Pharmacol. 2009 Apr 17;608(1-3):84-90. doi: 10.1016/j.ejphar.2009.02.023. Epub 2009 Feb 23. PMID: 19239910 4:Mechanisms involved in the cell cycle and apoptosis of HT-29 cells pre-treated with MK-886 prior to photodynamic therapy with hypericin. Kleban J, Mikes J, Horváth V, Sacková V, Hofmanová J, Kozubík A, Fedorocko P.J Photochem Photobiol B. 2008 Nov 13;93(2):108-18. doi: 10.1016/j.jphotobiol.2008.07.007. Epub 2008 Aug 6. PMID: 18771933 5:Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats. Daglar G, Karaca T, Yuksek YN, Gozalan U, Akbiyik F, Sokmensuer C, Gurel B, Kama NA.J Surg Res. 2009 May 1;153(1):31-8. doi: 10.1016/j.jss.2008.02.052. Epub 2008 Mar 26. PMID: 18656901 6:Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice. Uz T, Dimitrijevic N, Imbesi M, Manev H, Manev R.Neurosci Lett. 2008 May 9;436(2):269-72. doi: 10.1016/j.neulet.2008.03.041. Epub 2008 Mar 21. PMID: 18403121 Free PMC Article7:In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886). Biserni A, Giannessi F, Sciarroni AF, Milazzo FM, Maggi A, Ciana P.Mol Pharmacol. 2008 May;73(5):1434-43. doi: 10.1124/mol.107.042689. Epub 2008 Feb 21. PMID: 18292206 Free Article8:5-Lipoxygenase inhibitor MK-886 increases GluR1 phosphorylation in neuronal cultures in vitro and in the mouse cortex in vivo. Imbesi M, Zavoreo I, Uz T, Sharma RP, Dimitrijevic N, Manev H, Manev R.Brain Res. 2007 May 25;1147:148-53. Epub 2007 Feb 14. PMID: 17349982 9:Pre-treatment of HT-29 cells with 5-LOX inhibitor (MK-886) induces changes in cell cycle and increases apoptosis after photodynamic therapy with hypericin. Kleban J, Szilárdiová B, Mikes J, Horváth V, Sacková V, Brezáni P, Hofmanová J, Kozubík A, Fedorocko P.J Photochem Photobiol B. 2006 Aug 1;84(2):79-88. Epub 2006 Mar 20. PMID: 16545574 10:Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice. Jawien J, Gajda M, Rudling M, Mateuszuk L, Olszanecki R, Guzik TJ, Cichocki T, Chlopicki S, Korbut R.Eur J Clin Invest. 2006 Mar;36(3):141-6. PMID: 16506957