Research Projects

Protac (Proteolysing Targeting chimeras) represents a transformative advancement in drug discovery offering new therapeutic opportunities by addressing proteins that are traditionally considered ‘undruggable.’Repotrectinib (USFDA approved ROS1-positive metastatic non–small cell lung cancer drug) is designated as a breakthrough therapy designation (BTD) and discovery by Zai Lab (Shanghai) Co., Ltd. and Olutasidenib (recently Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) drug). Synthetic approaches adopted to synthesize repotrectinib and olutasidenib essentially require a multistep with 4 steps to get enantiopure intermediate using a toxic, expensive metal catalyst [Ru], and use of expensive substrate, (R)-(+)-2-methyl-2-propanesulfinamide, for imine formation in presence of methylmagnesium bromide (flammable) at -65 °C indicating requirement of a lot of energy. In addition, this synthetic process produces two diastereomers even after low-yielding multistep (seven) reaction. The current enzymatic process involves a two-step method utilizing transaminase to obtain enantiopure intermediates for Repotrectinib and Olutasidenib. Additionally, a three-step process employing a lipase enzyme has been proposed, which reduces the overall number of steps required for drug synthesis.This proposal aims to develop a new method for enzymatic synthesis of important intermediates used in Repotrectinib, Olutasidenib, PROTAC drugs, utilizing lipase. The focus is on creating efficient, sustainable, environmentally-friendly, and cost-effective processes for synthesizing enantiopure drugs and active pharmaceutical ingredients (APIs). Biocatalyst approaches are particularly valuable for their clean and green reactions, easy purification, minimal use of toxic chemicals, and ability to produce enantiopure chiral intermediates for chiral drugs.

Enzyme technology, Lipase, transaminase, PROTAC, Repotrectinib, Olutasidenib