Literature DB >> 8357985

A new class of leukotriene biosynthesis inhibitor: the development of MK-0591.

P Prasit1, M Belley, M Blouin, C Brideau, C Chan, S Charleson, J F Evans, R Frenette, J Y Gauthier, J Guay.   

Abstract

The evolution of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy+ ++)indol-2-yl]- 2,2-dimethylpropanoic acid), 12, a potent, orally active leukotriene biosynthesis inhibitor is described. MK-0591 is currently undergoing clinical evaluation as a potential agent for the treatment of asthma and inflammatory bowel disease. It acts through a novel mechanism by a specific interaction with a membrane protein, 5-lipoxygenase activating protein (FLAP), which has been shown to be essential for LT synthesis in inflammatory cells. A brief comparison of its biological activity with that of its progenitors MK-886 and L-674,636 is described.

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Year:  1993        PMID： 8357985

Source DB:  PubMed          Journal:  J Lipid Mediat        ISSN： 0921-8319


  5 in total

1.  Expression, purification and crystallization of human 5-lipoxygenase-activating protein with leukotriene-biosynthesis inhibitors.

Authors:  Shihua Xu; Brian M McKeever; Douglas Wisniewski; Douglas K Miller; Robert H Spencer; Lin Chu; Feroze Ujjainwalla; Ting Ting Yamin; Jilly F Evans; Joseph W Becker; Andrew D Ferguson
Journal:  Acta Crystallogr Sect F Struct Biol Cryst Commun       Date:  2007-11-30

2.  Inhibition of 5-lipoxygenase selectively triggers disruption of c-Myc signaling in prostate cancer cells.

Authors:  Sivalokanathan Sarveswaran; Debrup Chakraborty; Dhananjay Chitale; Rosalie Sears; Jagadananda Ghosh
Journal:  J Biol Chem       Date:  2014-12-24       Impact factor: 5.157

3.  MK591, a second generation leukotriene biosynthesis inhibitor, prevents invasion and induces apoptosis in the bone-invading C4-2B human prostate cancer cells: implications for the treatment of castration-resistant, bone-metastatic prostate cancer.

Authors:  Sivalokanathan Sarveswaran; Ritisha Ghosh; Shravan Morisetty; Jagadananda Ghosh
Journal:  PLoS One       Date:  2015-04-15       Impact factor: 3.240

4.  Inhibition of 5-lipoxygenase downregulates stemness and kills prostate cancer stem cells by triggering apoptosis via activation of c-Jun N-terminal kinase.

Authors:  Sivalokanathan Sarveswaran; Nadimpalli R S Varma; Shravan Morisetty; Jagadananda Ghosh
Journal:  Oncotarget       Date:  2019-01-11

5.  Pharmacological and genetic targeting of 5-lipoxygenase interrupts c-Myc oncogenic signaling and kills enzalutamide-resistant prostate cancer cells via apoptosis.

Authors:  Jitender Monga; Dhatchayini Subramani; Ajay Bharathan; Jagadananda Ghosh
Journal:  Sci Rep       Date:  2020-04-20       Impact factor: 4.379
  5 in total

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