Direct Keap1-kelch inhibitors as potential drug candidates for oxidative stress-orchestrated diseases: A review on In silico perspective

The recent outcry in the search for direct keap1 inhibitors requires a quicker and more effective drug discovery process which is an inherent property of the Computer Aided Drug Discovery (CADD) to bring drug candidates into the clinic for patient's use. This Keap1 (negative regulator of ARE master activator) is emerging as a therapeutic strategy to combat oxidative stress-orchestrated diseases. The advances in computer algorithm and compound databases require that we highlight the functionalities that this technology possesses that can be exploited to target Keap1-Nrf2 PPI. Therefore, in this review, we uncover the in silico approaches that had been exploited towards the identification of keap1 inhibition in the light of appropriate fitting with relevant amino acid residues, we found 3 and 16 other compounds that perfectly fit keap1 kelch pocket/domain. Our goal is to harness the parameters that could orchestrate keap1 surface druggability by utilizing hotspot regions for virtual fragment screening and identification of hotspot residues.

Automated summary

This study highlights the use of Computer Aided Drug Discovery (CADD) to identify Keap1 inhibitors, emphasizing the functionalities that can be exploited for targeting Keap1-Nrf2 PPI. Through computational methods, compounds perfectly fitting the keap1 kelch pocket/domain were found, opening possibilities for developing new drugs to treat diseases caused by oxidative stress.