Novel LXR/ER modulator as a polypharmacological agent against Breast Cancer

AMADO, L. D.; MEDRANO, P.; PECCI, A.; PALAVECINO RUIZ, M. D.; BURTON, G.; DANSEY, M. V.; MOSNA, M. J. ; CARCAGNO, A. L.

Mar del Plata

Congreso; LXIV reunión anual de la Sociedad Argentina de investigaciones clínicas; 2019

SAIC

Breast Cancer (BC) is a complex disorder due to multiple genes deregulation, which prompts a robust phenotype. The pharmacological paradigm of ?magic bullets?, targeting individual chemoreceptors, fails as redundant functions are activated and alternative compensatory signaling routes sustain the tumor phenotype, leading to immune escape. Polypharmacology arises as a new paradigm: designing multifunctional non-selective drugs that interact with several molecular targets. This approach would tackle several signaling and metabolic routes at the same time, with one drug, leading to new and more effective treatment against BC. Our hypothesis is that a dual antagonist of both, Estrogen Receptor (ER) and Liver X Receptor (LXR), would inhibit the ER canonical survival routes, but also would inhibit lipogenesis and Warburg effect through LXR antagonism. We performed a screening of different natural and synthetic oxysterols where Compound 1 (C1) emerged as a promising compound