A CHEMICAL SYSTEMS BIOLOGY APPROACH FOR IDENTIFYING OFF-TARGETS OF CALCITRIOL

Abstract

Drugs having off-targets other than their intended targets often result in side effects. Therefore the identification of possible off-targets during the process of drug design can prevent possible side-effects and rejections of the drugs during chemical trials thereby improving therapeutic actions of drugs. Calcitriol, an FDA approved therapeutic agent, is a Vitamin D3 Receptor inhibitor that is used for the treatment of psoriasis and to prevent low levels of calcium in bone disease. However, this drug has been reported to have certain side effects and complications such as bone pain, slow growth, heart rate changes (fast, slow, or uneven). Present in silico based study focuses on the identification of off-targets of Calcitriol using a computational biology approach. The crystal structure of VDR-Calcitriol complex (PDB ID:2HC4) was used for binding pocket similarity search to identify the putative off-targets of Calcitriol. These were further investigated using molecular docking approach. Analogs of Calcitriol were then investigated to make a more efficient drug with fewer side effects.