Rational approaches of drug design for the development of selective estrogen receptor modulators (SERMs), implicated in breast cancer

Abstract

Drug discovery and development have gained momentum due to the rational drug design by engaging computational tools and bioinformatics methodologies. Bioisosteric replacements and hybrid molecular approaches are the other inventive processes, used by medicinal chemists for the desired modifications of leads for clinical drug candidates. SERMs, ought to produce inhibitory activity in breast, uterus and agonist activity in other tissues, are beneficial for estrogen-like actions. ER subtypes α and β are hormone dependent modulators of intracellular signaling and gene expression, and development of ER selective ligands could be an effective approach for treatment of breast cancer. This report has critically investigated the possible designing considerations of SERMs, their in silico interactions, and potent pharmacophore generation approaches viz. indole, restricted benzothiophene [3, 2-b] indole, carborane, xanthendione, combretastatin A-4, organometallic heterocycles, OBHS-SAHA hybrids, benzopyranones, tetrahydroisoquinolines, Dig G derivatives and their specifications in drug design and development, to rationally improve the understanding in drug discovery. This also includes various strategies for the development of dual inhibitors for the management of antiestrogenic resistance.

Keywords: 17-β Estradiol and His524; Estrogen receptor; Helix-12; Ligand Binding Domain (LBD); Pharmacophore; SERMs.