Раковая наука и терапия

Metadichol ®. A Novel Inverse Agonist of Aryl Hydrocarbon Receptor (AHR) and NRF2 Inhibitor

Abstract

Raghavan PR

Metadichol ® a novel nano emulsion of lipid alcohols is an Inverse agonist of Vitamin D Receptor (VDR). In this communication, we show that Metadichol is an inverse agonist of the nuclear receptor AHR (Aryl Hydrocarbon receptor) and also an inhibitor of NRF2 (NF-E2-related factor-2) and is a transcription factor that is ubiquitously expressed at low levels in all human organs and regulates a primary cellular defense mechanism, tight regulation to maintain cellular homeostasis. AHR is highly expressed in a broad panel of tumors, AHR is induced by 2,3,7,8-tetrachloride-benzo-p-dioxin (TCDD) Metadichol® with inverse agonist against AHR could be potentially useful in the treatment of such diseases. Strong in vivo evidence suggests that TCDD can stimulate cross-talk between AHR and Nrf2. The constitutive up regulation of Nrf2 signaling appears to drive the cellular proliferation and resistance to chemotherapy in various cancers. Therefore, pharmacological inhibition of Nrf2 by Metadichol ® holds promise as a therapeutic strategy in chemo resistant forms of cancer.