Medicinal Chemistry

Our lab develops new chemical methodologies to mimic the diverse structural features found in natural products with the goal to capture their unique biological properties in drug-like scaffolds. Students in the lab with synthesize and test the new scaffolds in order to optimize the natural product mimics for potency, selectivity, cytotoxicity ADME, PK and PD properties. Using a battery of assays, no-go/go decisions will be made along the way as we evaluate the suitability of the compound for further evaluation.  Current programs are focused on novel therapeutics for multiple myelomaneurodegenerative diseases, and tuberculosis.

Some recent representative publications of different compound classes under development in our group are:

  • Substituted quinolines as noncovalent proteasome inhibitors, Bioorganic and Medicinal Chemistry201624, 2441-2450.
  • Inhibition of the human proteasome by imidazoline scaffolds. Journal of Medicinal Chemistry2013, 56, 5974-5978. *Article Highlighted in Science Business Exchange SciBX 6(28),  July 25, 2013
  • Noncompetitive modulation of the proteasome by imidazoline scaffolds overcomes bortezomib resistance and delays MM tumor growth in vivo. ACS Chemical Biology2013, 8, 578-587. *Article Highlighted: ACS Chemical Biology editors highlight article from Volume 8, Issue 3 and speak with author Jetze Tepe on itunes podcast, March 2013.
  • Radioprotection by hymenialdisine-derived checkpoint kinase 2 inhibitors. ACS Chemical Biology 20127, 172-184.
  • Synthesis and evaluation of debromohymenialdisine-derived Chk2 inhibitors. Bioorganic & Medicinal Chemistry 201220, 1475-1481.
  • Non-competitive inhibition of the human proteasome attenuates collagen-induced arthritis. Bioorganic & Medicinal Chemistry Letters 201222, 4816-4819.  
  • Structural activity relationship of functionalized trans-imidazolines as potent inhibitors of interleukin-6 production. Bioorganic & Medicinal Chemistry200917, 3093-3103.
  • Nuclear Factor-κB Mediated Inhibition of Cytokine Production by Imidazoline Scaffolds. Journal of Medicinal Chemistry 200952, 1302-1309. *Article highlighted in: Science-Business eXchange 2009, 2, 18.