Instructions

Two students are assigned to present one of the following topics. It is up to you whether one or both of you delivers the presentation.

For each topic, you can find one or two related research articles as well as relevant reviews. You do NOT have to present everything in these papers. Your goal is to introduce the general background, key results, and the central ideas of the articles. Please feel free to find more relevant studies/articles/materials through PubMed or Google if they help clarify the concepts or provide additional examples.  Ideally, one student will present the general background of the topic and the other will talk about specific findings and examples.

Molecules in Pharmacokinetics

OCT1 - PGx, Transporters, & Antidiabetic Drug

Organic Cation Transporters belongs an family of solute carriers (SLCs) are that found in liver, kidney, and intestine with broad specificity toward many drugs, toxins, and endogeneous compounds. See Jonker et al. and Koepsell et al. for reviews. A recent report in J. Clin Invest gives the first full description of the relevance of OCT SNPs for a widely used antidiabetic drug. See Reitman & Schadt for commentary.

MDR1 - Silent SNP Makes a Buzz

MDRs and ABC transporters are important molecules in ADME. See Gottesman et al. and Borst et al. for comprehensive reviews. A SCIENCE report from Gottesman's group showed that a silent SNP of MDR1 surprisingly can change the substrate specificity of the efflux pump.

Small Molecule Drug Discovery

Fragment-Based Drug Design

Structure-based drug design is usually used for fine tuning the hit compounds after they are found by high througput screen. A recent trendy approach in structure-based drug discovery is fragment-based drug design (reviewed by Hajduk et al. and Rees et al.), which has yielded promising results toward many targets including PDEs.

Drug-Like Molecules - Lipinsky's Rule of Five

Are you on the right track when you are in the middle of developing small molecule-based therapeutic compounds? Lipinski's Rule of Five published 10 years ago is a must-read. What are the recent trends and thoughts? See a very recent analysis by Leeson et al. from AstraZeneca and Gleeson from GlaxoSmithKline.

High Througput Screen

HTS is a commonly used approach in modern drug discovery. Walter et al. and Ingeles et al. reviewed the design and practice of HTS assays. A short PNAS paper from NIH added another dimension to HTS.

Target Deconvolution

If you find some hits in a cell-based HTS assay, how do you find their targets? See a very recent review on target deconvolution. A good example can be found in a study by Chen et al..

New Targets and Challenges

Targeting Kinases - Anti-Cancer Drug & The Story of Gleevec

As key players in cell proliferation, kinases represent a family of attractive drug targets treating cancers. Gleevec is one of the few successful examples of anti-cancer kinase inhibitors. Structural studies explained how and why it works against CML. Resistance, nevertheless, emerged. A second wave of new drugs overcoming resistance were developed. The story continues.....

Targeting Protein Interface - A Challenge in the Post-Proteomic Era

Protein-protein interactions are essential for signal transduction and almost all cellular functions. However, protein-protein interface is not an easy target. The current progress and approaches are discussed by Wells et al. (also see an older article). Nutlin is a well-known example of success.