The development of new pharmacologic agents requires extensive explorations of the chemical space to transform an initial hit compound into a potent and selective chemical probe, or optimize it into a chemical entity with desirable drug-like properties. Our laboratory research interests are in the broadly defined fields of organic synthesis and medicinal chemistry. Our efforts over the past twenty-five years have been focused on the design and the diversity-oriented synthesis of small molecule, peptidomimetic, peptide and cyclic peptide combinatorial libraries and their application in drug discovery. The small molecules libraries are designed to follow known drug-likeness rules including “Lipinski’s Rule of Five”. Our team aims to discover and synthesize biologically active small molecules as research tools and drug leads. Our compound library collection of small molecule compounds consists of more than 35 million compounds designed around 85 molecular scaffolds systematically arranged in positional scanning and scaffold ranking formats. These formats allow for the analysis of millions of compounds through the use of just hundreds to thousands of samples. The large numbers of chemical libraries of linear and cyclic peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural product-like organic molecules provide for an exponential increase in screening efficiencies, rich initial SAR, and a unique chemical space while maintaining critical drug like chemical properties. In addition to our mixture-based libraries, we have a large selection of drug like individual small molecule heterocyclic compounds (>10,000) carefully selected from lead-like chemotypes. These compounds are available for high-throughput screening (HTS) and high-content screening (HCS). All compounds have been plated in 96-well plates at 10 mM concentration in DMSO and can be swiftly supplied in different customized formats. As evidenced by the group publication’s record, the synthetic libraries developed have impacted numerous fields of human health, including cancer, inflammation, pain, diabetes, CNS disorders, antimalarial, and bacterial resistance. Dr. Nefzi research has been supported by the National Institute of Health (NIH), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Cancer Institute (NCI), the National Institute of Aging (NIA) and the National Science Foundation (NSF).
Diverse small molecule, peptide, cyclic peptide and peptidomimetic libraries for phenotypic screening, deconvolution of active libraries for identification of active compounds, structure activity relationship (SAR) development: hit to lead optimization, target-based approach for the design and synthesis of “drug-like” molecules, target-based drug design integrated with molecular modeling, scale-up to support in vitro and in vivo efficacy models, development of robust synthetic procedures for scale-up, analytical chemistry support, including drug stability, solubility and structural determinations.