Synonym
MK-886 sodium salt
IUPAC/Chemical Name
1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-α,α-dimethyl-5-(1-methylethyl)-1H-indole-2-propanoic acid, sodium salt
InChi Key
CBNCIYNCWVGEKJ-UHFFFAOYSA-M
InChi Code
InChI=1S/C27H34ClNO2S.Na/c1-17(2)19-10-13-22-21(14-19)24(32-26(3,4)5)23(15-27(6,7)25(30)31)29(22)16-18-8-11-20(28)12-9-18;/h8-14,17H,15-16H2,1-7H3,(H,30,31);/q;+1/p-1
SMILES Code
CC(C)(C([O-])=O)CC1=C(SC(C)(C)C)C2=CC(C(C)C)=CC=C2N1CC3=CC=C(Cl)C=C3.[Na+]
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
Shelf Life
>3 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).
HS Tariff Code
2934.99.9001
Biological target:
MK-886 sodium salt inhibits leukotriene biosynthesis in leukocytes.
In vitro activity:
The ability of MK886 to affect PPAR-α, -β and -γ activity was assessed using transient transfection reporter assays in CV-1 and
keratinocyte 308 cell lines, and a stable transfection system in CV-1 cells. In all systems examined, 10 µM MK886 was able to inhibit Wy14,643 activation of PPARα by approx. 80% (Table 1). A dose–response study in keratinocyte 308 cells showed inhibition of 30³5, 65³7 and 70³8% at doses of 0.5, 1 and 5 µM MK886 respectively (n¯9). At doses between 10 and 20 µM, PPARα reporter assay activity levels were actually below the basal activity recorded in non-treated controls, suggesting inhibition of the endogenous PPARα. At doses over 20 µM, toxicity of MK886 precluded any useful measurements. MK886 also decreased PPARα activation by fatty acids in the stable transfection system (results not shown), indicating that its effect is not specific to activation by Wy14,643. Effects of MK886 on PPARβ activated with bezafibrate were substantial (48% inhibition) using the stable transfection assay in CV-1 cells, but were not evident using the transient transfection reporter assay in CV-1 cells or keratinocytes (Table 1), perhaps because of low reporter activity. Inhibition by MK886 of PPARγ activated with 15-deoxy-∆"#,"%-prostaglandin J# was also substantially lower than that seen with PPARα. The large standard error with PPARγ in the stable transfection system is a consequence of the very low activation achieved. The effect of MK886 on PPARα was also investigated in A549 human lung adenocarcinoma cells. There was no enhancement in reporter activity with activators of PPARβ and PPARγ using this cell line. As a result, it was not feasible to look at the
effect of MK886 on PPARβ or PPARγ in this system. However, 20 µM MK886 did inhibit PPARα by 73% relative to levels seen following activation with 100 µM Wy14,643 (Table 2). Similar levels of inhibition were seen if activation was achieved with 50 µM Wy14,643 (results not shown).
Reference: Biochem J. 2001 Jun 15;356(Pt 3):899-906. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/11389700/
In vivo activity:
When administered in vivo MK-886 (L-663,536) was a potent inhibitor of antigen-induced dyspnea in inbred rats pretreated with methysergide (ED50, 0.036 mg/kg p.o.) and of Ascaris-induced bronchoconstriction in squirrel monkeys (1 mg/kg p.o.). 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), a model of leukotriene excretion in rat bile following antigen provocation, and a model in the guinea-pig ear where leukotriene synthesis was induced by topical challenge with ionophore A23187 (ED50, 2.5 mg/kg p.o. and 0.6 micrograms topically).
Reference: Can J Physiol Pharmacol. 1989 May;67(5):456-64. https://cdnsciencepub.com/doi/10.1139/y89-073?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
60.72 |
| DMF:PBS (pH 7.2) (1:4) |
0.2 |
0.40 |
| DMSO |
20.0 |
40.48 |
| Ethanol |
20.0 |
40.48 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
494.07
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kehrer JP, Biswal SS, La E, Thuillier P, Datta K, Fischer SM, Vanden Heuvel JP. Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J. 2001 Jun 15;356(Pt 3):899-906. doi: 10.1042/0264-6021:3560899. PMID: 11389700; PMCID: PMC1221919.
2. Gillard J, Ford-Hutchinson AW, Chan C, Charleson S, Denis D, Foster A, Fortin R, Leger S, McFarlane CS, Morton H, et al. L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1989 May;67(5):456-64. doi: 10.1139/y89-073. PMID: 2548691.
In vitro protocol:
1. Kehrer JP, Biswal SS, La E, Thuillier P, Datta K, Fischer SM, Vanden Heuvel JP. Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J. 2001 Jun 15;356(Pt 3):899-906. doi: 10.1042/0264-6021:3560899. PMID: 11389700; PMCID: PMC1221919.
2. Gillard J, Ford-Hutchinson AW, Chan C, Charleson S, Denis D, Foster A, Fortin R, Leger S, McFarlane CS, Morton H, et al. L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1989 May;67(5):456-64. doi: 10.1139/y89-073. PMID: 2548691.
In vivo protocol:
1. Gillard J, Ford-Hutchinson AW, Chan C, Charleson S, Denis D, Foster A, Fortin R, Leger S, McFarlane CS, Morton H, et al. L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1989 May;67(5):456-64. doi: 10.1139/y89-073. PMID: 2548691.
1. Ford-Hutchinson, A.W., Gresser, M., and Young, R.N. 5-Lipoxygenase. Annual Reviews of Biochemistry 63, 383-417 (1994).
2. Abramovitz, M., Wong, E., Cox, M.E., et al. 5-Lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase. European Journal of Biochemistry 215, 105-111 (1993).
3. Dixon, R.A.F., Diehl, R.E., Opas, E., et al. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature 343, 282-284 (1990).
