IIT Kanpur Researchers Reveal New Insights into Cholesterol-Lowering Drug Mechanisms

Kanpur: Researchers at the Indian Institute of Technology Kanpur's Department of Biological Sciences and Bioengineering have made significant strides in understanding the molecular workings of cholesterol-lowering drugs like Niacin. By employing cutting-edge cryogenic-electron microscopy (cryo-EM) technology, the team, led by Prof. Arun K. Shukla, successfully visualized the key receptor molecule activated by Niacin and related medications.

Niacin, commonly prescribed to reduce bad cholesterol and triglycerides while boosting good cholesterol, often triggers adverse effects such as skin redness and itching. These side effects, known as flushing responses, frequently prompt patients to discontinue treatment, adversely affecting their cholesterol levels, explained Prof. Shukla.

The study sheds light on the Hydroxycarboxylic acid receptor 2 (HCA2), also recognized as the niacin receptor or GPR109A. This receptor plays a crucial role in halting fat-related and artery-clogging processes. Activation of the HCA2 receptor can widen blood vessels, leading to the red, flushing skin reaction experienced by some patients taking cholesterol-lowering drugs like niacin.

Prof. Shukla emphasized, "The visualization of the receptor molecule GPR109A's interaction with Niacin at the molecular level lays the groundwork for creating new drugs that maintain efficacy while minimizing undesirable reactions." He also noted the potential for developing related medications for cholesterol management and other conditions like multiple sclerosis.

Prof. S. Ganesh, Director of IIT Kanpur, hailed the study as a breakthrough in deepening the understanding of drug-receptor interactions, paving the way for the design of improved therapeutic agents. He commended the institute's commitment to addressing real-world health challenges through innovative research, underscoring the high standards of research and development at IIT Kanpur.

Supported by the Science and Engineering Research Board (SERB), the study, spearheaded by Prof. Arun K Shukla, involved a team of researchers including Dr. Manish Yadav, Ms. Parishmita Sarma, Mr. Jagannath Maharana, Mr. Manisankar Ganguly, Ms. Sudha Mishra, Ms. Annu Dalal, Mr. Nashrah Zaidi, Mr. Sayantan Saha, Ms. Gargi Mahajan, Mr. Vinay Singh, Ms. Saloni Sharma, and Dr. Ramanuj Banerjee.

The research findings, published in the prestigious international journal Nature Communications, offer promising avenues for advancing drug development and enhancing patient outcomes in cholesterol management. [Link to the study]