New Delhi: A new smart cancer drug, developed by scientists from the Institute of Advanced Study in Science and Technology and IIT-Guwahati, is designed to switch on primarily inside cancer cells and could potentially offer a more targeted alternative to traditional chemotherapy.
The drug, RK-251, was developed by IASST’s Dr Asis Bala and IIT-Guwahati’s Dr KP Bhabak. It is designed to activate primarily in cancer cells while having much less effect on healthy cells.
“Cancer cells often produce high levels of reactive oxygen species (ROS), which are harmful molecules. When RK-251 enters a cancer cell, the high ROS levels trigger the drug’s activation, releasing a powerful anticancer compound called ‘NBDHEX’. This compound blocks target proteins that many cancer cells use to survive and resist treatment,” a statement issued by the Department of Science and Technology, which funds IASST, said.
The statement said that in preclinical studies, RK-251 showed strong activity against aggressive triple-negative breast cancer cells, with much less effect on healthy cells.
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How does the drug work?
In a study published in the Journal of Medicinal Chemistry, scientists explained that many cancer cells produce high amounts of an enzyme called GSTP1. This enzyme can help cancer cells survive by neutralising certain anticancer drugs.
This means that blocking the GSTP1 enzyme could potentially make cancer cells more vulnerable. Currently, an experimental drug called NBDHEX is a potent GSTP1 inhibitor. However, it does not dissolve well in water and is poorly absorbed by the body, making it difficult to use effectively as a medicine.
Researchers from IASST and IIT-Guwahati have turned NBDHEX into the RK-251 prodrug — an inactive form of a drug designed to become active under specific conditions.
Cancer cells have higher levels of reactive oxygen species (ROS), which are chemically reactive molecules produced during cellular processes. RK-251 is designed so that these higher ROS levels can act as a chemical trigger. Once it enters a cancer cell — an ROS-rich environment — the ROS activates RK-251, causing the molecule to break apart and release NBDHEX. The result is inhibition of GSTP1.
RK-251 also carries a fluorescent molecule called QCy7. When the prodrug is activated and releases its components, it produces near-infrared fluorescence. Under these conditions, NBDHEX is released, inhibiting GSTP1 and attacking cancer cells, while the fluorescence allows researchers to see that the drug has been activated.
This is called a theranostic approach, which combines therapy and diagnostics or imaging in one system.
“The behavioural study of the developed candidate drug in zebrafish embryos (Danio rerio) also showed no obvious signs of toxicity and exhibited the desired fluorescence in the presence of reactive oxygen species (ROS), suggesting the drug may be safe for further research and validation,” the study said.
Researchers also stressed that while the findings are promising, more studies are needed before the technology can be tested in patients.
(Edited by Prashant Dixit)