Research Areas

Ongoing Projects

• Rational drug design, Synthesis & Evaluation

• Targeted Protein Degradation

• Medicinal Chemistry and Drug Design

Rational Drug Design, Synthesis & Evaluation

Optimizing drug discovery programs is crucial for the development of effective and safe medications. At our lab, one of our most effective strategies involves identifying and implementing structural modifications in lead compounds to enhance their potency. Our work highlights the significance of molecular modification in the quest to discover new classes of lead compounds with superior pharmacotherapeutic activity. By meticulously altering the molecular structure of lead compounds, we can pinpoint modifications that result in enhanced biological activity and reduced toxicity. This focused approach not only streamlines the drug development process but also minimizes the need for extensive synthetic work, which can be both time-consuming and costly.

The necessity of our approach lies in its potential to revolutionize the drug discovery landscape. Traditional drug development methods often involve a trial-and-error approach, requiring the synthesis and testing of numerous compounds, which can be inefficient and resource-intensive. In contrast, our molecular modification techniques allow for a more targeted and rational design of lead compounds, increasing the likelihood of discovering more effective and safer medications. By leveraging molecular modification, we are developing drugs that not only exhibit higher potency but also possess a better safety profile, ultimately improving patient outcomes and advancing therapeutic innovations.

Targeted Protein Degradation

Protein overexpression is a hallmark of many diseases, including cancer (e.g., HER2 in breast cancer, EGFR in lung cancer), neurodegenerative disorders (e.g., amyloid-beta in Alzheimer's), viral infections (e.g., HIV-1 protease), autoimmune diseases (e.g., TNF-alpha in rheumatoid arthritis), cardiovascular conditions (e.g., PCSK9 in hypercholesterolemia), fibrotic diseases (e.g., TGF-beta), and metabolic disorders (e.g., insulin receptor substrates in type 2 diabetes). Targeted protein degradation using PROTACs (Proteolysis Targeting Chimeras) offers a revolutionary approach to addressing these pathologies.

PROTACs are bifunctional molecules designed to harness the cells natural protein degradation machinery. They consist of two active domains connected by a linker: one domain binds to the target protein, while the other recruits an E3 ubiquitin ligase. This dual binding facilitates the ubiquitination and subsequent degradation of the target protein by the proteasome, effectively removing the protein from the cell. Our research lab is actively engaged in exploring the revolutionary field of Proteolysis Targeting Chimeras (PROTACs), an approach that redefines therapeutic strategies by targeting and eliminating disease-associated proteins previously considered as undruggable. PROTACs, by leveraging the cell’s natural protein degradation machinery, offer a potent and durable solution, opening new avenues for drug discovery and development across a wide range of diseases. We are focusing on developing PROTACs against a plethora of oncotargets overexpressed in an array of cancers. 

Traditional drug therapies often fall short in effectively targeting these proteins, leaving significant gaps in treatment efficacy. PROTACs address this challenge by leveraging the cell’s natural protein degradation machinery, offering a potent and durable solution that opens new avenues for drug discovery and development across a wide range of diseases. By enabling the complete removal of malfunctioning proteins, PROTACs can enhance the effectiveness of treatments, reduce side effects, and provide solutions for diseases that currently lack effective therapies.

Medicinal Chemistry & Drug Design

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that methylates nicotinamide (NA) to generate N-methyl nicotinamide. Since its discovery 70 years ago, NNMT's role has expanded from metabolic functions to being implicated in various diseases, including multiple cancers. Overexpression of NNMT is linked to cancer progression and metabolic disorders, positioning it as a promising therapeutic target. Despite substantial evidence supporting NNMT as a viable target, the development of cell-active inhibitors remains insufficient. 

Our drug design efforts focus on creating small molecule inhibitors and modulators that can specifically inhibit NNMT activity without off-target effects. We are employing various computational approaches to address challenges related to selectivity and pharmacokinetics, which enhance the identification and refinement of novel inhibitors. In the future, our work aims to accelerate the development of NNMT-targeted therapies for various diseases.