Research interest
Of the
Our lab research interests converge at the interface of chemistry and biology aimed at discovering new therapeutics and unravelling new druggable targets in disease phenotypes. We will exploit the potential of phenotypic screening and chemoproteomics for drug discovery and uncovering the mechanistic targets of our lead small molecules.
Recent success of covalent therapeutics that target disease-relevant proteins in cancer and bacteria led to the discovery of several potent and effective therapeutics. The discovery of small-molecule inhibitors capable of irreversibly modifying drug targets and emerging into potential therapeutics dates back to the 1890s, when aspirin was discovered to induce anti-inflammatory effects in humans via irreversible modification of cyclooxygenase-I. In the 1920s, penicillin was discovered as a powerful broad-spectrum antibacterial agent that covalently inhibits a cell wall-biosynthetic enzyme, DD-carboxypeptidase, in bacteria. While these two historical drugs are extensively used to treat diseases, their use is jeopardized due to the toxicity associated with covalent inhibition of undesired target proteins. Besides, the spread of drug resistance in both cancer and bacteria to almost all existing therapeutics warrants complementary research strategies and new drug targets. Therefore, a hypothesis-driven approach that involves target-based drug design and a discovery-driven strategy comprising high-throughput screening of in-house synthesized small molecules in disease phenotypes are considered powerful alternatives and are the major focus of our lab.
Our lab specifically focuses on developing covalent small-molecule-based ferroptosis inducers that target glutathione perxidase-4. Further, we build structurally new molecules with the intention of identifying new druggable targets in cancer phenotypes.
In parallel to covalent therapeutics, our lab is working on developing trigger-inducible small molecule-based proteolysis activating chimeras (PROTACs) for driving degradation of protein of interest, organelles and proteins assemblies in disease phenotypes.