Computational Design of Novel Pyridine derivative as Potent Inhibitors of Insulin Receptor (IR) as Potential Anti-cancer Agent

Abstract

Modern cancer chemotherapy places a strong emphasis on developing target-based strategies rather than traditional ones due to advances in biochemistry, advanced exploitation of knowledge regarding genetics, genomes and successful research about various forms of human cancer. Protein tyrosine kinases (PTKs) are the most explored of the numerous targets that have been found, confirmed, and inhibited at various cancer hallmarks. Owing to their synthetic accessibility, favorable pharmacokinetic and pharmacodynamic optimization potential—including absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles—oral bioavailability, reduced off-target effects, and cost efficiency, small-molecule inhibitors of IGF-1R have emerged as prominent candidates in recent therapeutic research. The Insilco techniques are in use now-a days can affects the entire drug development process as identifying and discovering new potential drug is time and cost effective. Here, we are applying multiple Insilco techniques to examine IR inhibition activity. To find a powerful molecule, we employed the best pharmacophore and the structure-based pharmacophore as 3D queries. Following lead generation and optimisation using Structure-Based Drug Design (SBDD), 100 novel derivatives were created. Molecular docking experiments were then conducted to anticipate interactions and pinpoint structural characteristics. Drug-likeness and ADMET tests were also used to evaluate pharmacokinetics features. According to Swiss ADME and docking investigations, only the three L12, L50, and L6 exhibited the best performance and were selected for additional processing. They were also thought to be appropriate for high-grade IR inhibitors. Further, directional approach is also need in clinical trials and commercialization.