From Lab Bench to Your Medicine Cabinet

Week 2 – Natural products
Paper to discuss
Natural product leads for drug discovery: Isolation, synthesis and biological evaluation of 6-cyano-5-methoxyindolo[2,3-a]carbazole based ligands as antibacterial agents. Songpo Guo, Suresh K. Tipparaju, Scott D. Pegan, Baojie Wan, Shunyan Moa, Jimmy Orjala, Andrew D. Mesecar, Scott G. Franzblau, Alan P. Kozikowski
Bioorganic & Medicinal Chemistry 17:7126–7130 (2009).
Helpful Review
Better antibiotics through chemistry.
Simon Frantz
Nature Reviews Drug Discovery 3:900-900 (2004).
Drug discovery and natural products: end of an era or an endless frontier?
Li JW, Vederas JC.
Science 325:161-165 (2009).
In-class Discussion Questions

Week 3 – Fragment based screening
Paper to discuss
Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site. Larry R. McLean, Ying Zhang, Hua Li, Yong-Mi Choi, Zuoning Han, Roy J. Vaz, Yi Li.
Bioorganic & Medicinal Chemistry Letters 20:1821–1824 (2010).
Helpful Review
A decade of fragment-based drug design: strategic advances and lessons learned
Philip J. Hajduk and Jonathan Greer
Nature Reviews Drug Discovery 6:211-219 (2007).
Recent progress in fragment-based lead discovery
Michele N Schulz and Roderick E Hubbard
Current Opinion in Pharmacology 9:615–621 (2009).
In-class Discussion Questions

Week 4 – Proteomics
Paper to discuss
Identification of tumor-associated, MHC class II restricted phosphopeptides as targets for immunotherapy. Florence R. Depontieu, Jie Qian, Angela L. Zarling, Tracee L. McMiller, Theresa M. Salay, Andrew Norris, A. Michelle English, Jeffrey Shabanowitz, Victor H. Engelhard, Donald F. Hunt, and Suzanne L. Topaliana. Proc Natl Acad Sci U S A. 106:12073–12078 (2009).
Helpful Review
Proteomic methods for drug target discovery
Lekha Sleno and Andrew Emili
Current Opinion in Chemical Biology 12:46–54 (2008).
Antibody-based identification of cell surface antigens: targets for cancer therapy
Deryk T Loo and Jennie P Mather
Current Opinion in Pharmacology 8:627–631 (2008).
Also see for a quick review on T cell/MHC I and for an introduction on antitumor immunity.
In-class Discussion Questions

Week 5 – Combinatorial approaches
Paper to discuss
A Fragment-Based Approach to Probing Adenosine Recognition Sites by Using Dynamic Combinatorial Chemistry. Duncan E. Scott, Gwen J. Dawes, Michiyo Ando, Chris Abell, and Alessio Ciulli.
ChemBioChem 10:2772 – 2779 (2009).
Helpful Review
Combinatorial chemistry in cancer research
A. Messeguer and N. Cortés
Clinical & translational oncology 9:83 – 92 (2007).
In-class Discussion Questions

Week 6 – Rational (structure based) design
Paper to discuss
Enhancement of Hydrophobic Interactions and Hydrogen Bond Strength by Cooperativity: Synthesis, Modeling, and Molecular Dynamics Simulations of a Congeneric Series of Thrombin Inhibitors.
Laveena Muley, Bernhard Baum, Michael Smolinski, Marek Freindorf, Andreas Heine, Gerhard Klebe, and David G. Hangauer.
J. Med. Chem. 53:2126–2135 (2010).
Helpful Review
Rational drug design
Soma Mandal, Mee’nal Moudgil, Sanat K. Mandal
European Journal of Pharmacology 625:90–100 (2009).
In-class Discussion Questions

Week 7 – siRNA
Paper to discuss
Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron. Ying Poi Liu, Joost Haasnoot, Olivier ter Brake, Ben Berkhout* and Pavlina Konstantinova.
Nucleic Acids Research 36:2811–2824 (2008).
Helpful Review
The promises and pitfalls of RNA-interference-based therapeutics.
Daniela Castanotto & John J. Rossi
Nature 457:426-433 (2009).
In-class Discussion Questions

Week 8 – Gene therapy
Paper to discuss
Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Aravind Asokan, Julia C Conway, Jana L Phillips, Chengwen Li, Julia Hegge, Rebecca Sinnott, Swati Yadav, Nina DiPrimio, Hyun-Joo Nam, Mavis Agbandje-McKenna, Scott McPhee, Jon Wolff & R Jude Samulski.
Nature Biotechnology 28:79 – 82 (2010).
Helpful Review
Gene therapy: The first two decades and the current state-of-the-art. Terence Flotte.
J. Cell. Physiol. 213:301-305 (2007).
In-class Discussion Questions

Week 9 – Pharmacokinetics
Paper to discuss
Integrated in vitro analysis for the in vivo prediction of cytochrome P450-mediated drug-drug interactions.
Dermot F. McGinnity, Nigel J. Waters, James Tucker, Robert J. Riley.
Drug metabolism and distribution. 36:1126-1134 (2008).
Helpful Review
Chapter 9 of Real world drug discovery: a chemist’s guide to biotech and pharmaceutical research by Robert M. Rydzewski.
In-class Discussion Questions

Week 10-Liposomal Delivery
Paper to discuss
Novel peptide ligand directs liposomes toward EGF-R high-expressing cancer cells in vitro and in vivo
Shuxian Song, Dan Liu, Jinliang Peng, Hongwei Deng, Yan Guo, Lisa X. Xu, Andrew D. Miller, and Yuhong Xu
The FASEB journal 5:1396-1404 (2009).
Helpful Review
Liposomes and nanoparticles:nanosized vehicles for drug delivery in cancer
Yogeshkumar Malam, Marilena Loizidou and Alexander M. Seifalian
Trends in pharmacological sciences. 30:592-599 (2009).
In-class Discussion Questions

Week 11 – Ethics
Papers to discuss
Science, pharmacoeconomics and ethics in drug R&D: a sustainable future scenario?
Paolo Preziosi
Nature Reviews Drug Discovery 3:521- 526 (2004).
From chemical to drug: neurodegeneration and drug screening and the ethics of clinical trials.
Jill Heemskerk, Allan J. Tobin, and Bernard Ravina
Nature Neuroscience (supplement) 5:1027 – 1029 (2002).
In-class Discussion Questions