Medicinal chemistry and chemical biology

The Wang Lab focuses on drug design, assay development, and drug resistance, with a strong emphasis on the development of first-in-class small-molecule drug candidates to support target validation and translational research. Our multidisciplinary approach integrates structure-based drug design, ultra-large virtual screening, machine learning-guided prioritization, direct-to-biology parallel synthesis, mechanism-informed assay development, pharmacokinetic profiling and optimization, and in vivo efficacy studies in animal models. We are particularly interested in discovering and validating novel drug targets through the design of chemical probes, including covalent inhibitors, PROTACs, and molecular glues, to interrogate protein function and therapeutic potential.

As academic drug hunters, we aim to bridge basic science and translational medicine by elucidating new mechanisms of action and applying cutting-edge chemical biology strategies to accelerate antiviral and therapeutic discovery. Notable accomplishments from our lab include the identification of dichloroacetamide as a novel cysteine-reactive warhead, the development of the first-in-class SARS-CoV-2 papain-like protease (PLpro) inhibitors with demonstrated in vivo antiviral efficacy, and the prediction and validation of clinically relevant drug-resistant mutations against nirmatrelvir, a key COVID-19 therapeutic.

While our foundational work has centered on antiviral research, we are actively expanding our expertise to address unmet medical needs in chronic diseases such as cancer, pain, and neurodegenerative disorders. Our long-term goal is to enable the development of mechanistically novel therapeutics with improved efficacy, selectivity, and resistance profiles across a broad spectrum of diseases.

We currently have multiple openings at all levels (postdoc, graduate student, technician, and undergraduate). Please contact Dr. Wang (junwang@pharmacy.rutgers.edu) if you are interested in exploring research opportunities in the Wang Laboratory. Candidates with background or interest in medicinal chemistry, pharmacology, assay development, high-throughput screening, and molecular biology are all welcomed!

PDB structures

SARS-CoV-2 Mpro inhibitors: 6WTT (Mpro+GC376), 6XA4 (Mpro+UAWJ241), 6XFN (Mpro+UAWJ243),  6XBG (Mpro+UAWJ246), 6XBH (Mpro+UAWJ247), 6XBI (Mpro+UAWJ248), 7KX5 (Mpro+Jun8-76-3R), 7LYH (Mpro+UAWJ9-36-1), 7LYI (Mpro+UAWJ9-36-3), 7RN0 (Mpro+Jun9-57-3R), 7RN1 (Mpro+Jun9-62-2R). 7TOB (Omicron Mpro P132H+GC376), 8D4P (Mpro+Jun10-90-3-C1), 8FTL (Mpro+Jun89-3-C1), 8FIV (Mpro+Jun10541R), 8FIW (Mpro+Jun10221)

SARS-CoV-2 Mpro mutants: 8SPJ (N28T), 8D4J (H172Y apo), 8D4K (H172Y-GC376), 8EHJ (H172Q), 8D4L (S144A), 8D4M (S144A-GC376), 8D4N (E166Q apo), 8DFN (H164N apo), 8DD1 (H164N-GC376), 8SXO (H164I),  8DFE (S144L apo), 8DD9 (S144L-GC376), 8D4L (S144A), 8D4M (S144A+GC376), 8DGB (Q192T-GC376), 8DCZ (M165Y-nirmatrelvir), 8EHJ (H172Q), 8EHK (T135I), 8EHL (S144M), 8EHM (S144F), 7TOB (P132H+GC376), 8SPJ (N28T), 8SXO (H164I)

SARS-CoV-2 PLpro inhibitors: 7JRN (PLpro+GRL0617), 7RZC (PLpro+Jun9-84-3), 7SQE (PLpro+Jun9-84-3), 7SDR (PLpro+Jun9-72-2).

EV-D68 2A protease: 7JRE (2A C107A), 7LW2 (N84T),

Influenza M2 channel blockers: 2KQT (M2 WT+Amt), 2LY0 (M2 S31N+M2WJ332), 2MUV (M2 S31N+BC035), 2MUW (M2 WT+BC035).