The nuclear receptors, liver X receptor-α and –β (LXRα and LXRβ), were originally identified as orphan members of the nuclear receptor (NR) superfamily that function as heterodimers with the retinoid X receptor (RXR). ). LXRα is primarily expressed in the liver, kidneys, intestines, and adipose tissues while LXRβ is widely expressed. Both LXRα and LXRβ play important roles in cholesterol homeostasis and lipid metabolism, and have been implicated in the pathology of several diseases including atherosclerosis, cancer, and obesity. Agonists induce a conformational change that results in an increase in transcription of a target gene. An antagonist blocks the action of an agonist and may cause a shift in potency or efficacy, but causes no change in receptor activity itself. An inverse agonist has the ability to induce a unique conformational change that results in repression of target gene transcription, most likely due to the recruitment of corepressors. Burris et al. has previously identified novel synthetic LXR Inverse Agonists (SR 9238 and SR 9243) which displayed the ability to suppress NASH and Liver Fibrosis. In this current endeavor, we exploited the structure based computational approach to investigate novel tetrahydro isoquinoline templates as LXR modulators.

Novel tetrahydro isoquinoline derivatives as LXR modulators

253rd National Meeting (2017)

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