5-LIPOXYGENASE INHIBITOR MK591

General description

A cell permeable, bioavailable, 2-indolealkanoic acid derived compound that acts as a highly potent and selective inhibitor of leukotriene biosynthesis (IC₅₀ = 3.1 nM in intact human polymorphonuclear leukocytes). Shown to inhibit 5-lipoxygenase (5-LOX) activity in LNCaP prostate cancer cells by high-affinity binding to 5-lipoxygenase activating protein (FLAP; IC₅₀ = 1.6 nM in a FLAP binding assay). Induces apoptosis in LNCaP cells without blocking PI 3 kinase-Akt or ERK activities. Also shown to induce rapid phosphorylation of c-Jun N-terminal Kinase (JNK) and indirectly block PKCε activity. Suppresses the deposition of Ab1-40 and Ab1-42 peptides in Tg2576 mice (~40 mg/kg/day in diet) with concomitant reduction in the levels of presenilin 1, nicastrin, APH-1 and Pen-2, but without affecting notch signaling. Exhibits desirable pharmacokinetic properties with tmax of 3.3 h and t1/2 = ~12 h.

A cell permeable, bioavailable, 2-indolealkanoic acid derived compound that acts as a highly potent and selective inhibitor of leukotriene biosynthesis (IC₅₀ = 3.1 nM in intact human polymorphonuclear leukocytes). Shown to inhibit 5-lipoxygenase (5-LOX) activity in LNCaP prostate cancer cells by high-affinity binding to 5-lipoxygenase activating protein (FLAP; IC₅₀ = 1.6 nM in a FLAP binding assay). Induces apoptosis in LNCaP cells without blocking PI 3 kinase-Akt or ERK activities. Also shown to induce rapid phosphorylation of c-Jun N-terminal Kinase (JNK) and indirectly block PKCε activity. Suppresses the deposition of Ab1-40 and Ab1-42 peptides in Tg2576 mice (~40 mg/kg/day in diet) with concomitant reduction in the levels of presenilin 1, nicastrin, APH-1 and Pen-2, but without affecting notch signaling. Exhibits desirable pharmacokinetic properties with tmax of 3.3 h and t1/2 = ~12 h.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

MK591; MK0591; 5-LOX inhibitor, 5- Lipoxygenase inhibitor, FLAP

Biochem/physiol Actions

Cell permeable: yes

Primary Target
FLAP

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Chu, J., et al. 2012. J. Neuroinflamm.9, 127.
Sarveswaran, S., et al. 2011. Bioch. Biophy. Acta.1813, 2108.

Sarveswaran, S., et al. 2010. Cancer Lett.291, 167.
Uematsu, T., et al. 1995. Br. J. Clin. Pharm.40, 59.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany