Metabolism in Lead Optimization - Triad Drug Discovery Group
Does it take exquisite experimental design or simply luck to identify a lead compound, take it through pre-clinical and clinical studies, and ultimately provide a safe and effective drug in humans. The answer is both…knowing the best way to screen lead compounds in cells and animals gets closer to predicting how it might react in humans but in the end it still takes a lot of luck to produce the next blockbuster drug.
Murty Arimilli from TMT Pharma Inc spoke about “Metabolism in Lead Optimization” at the March 12, 2009 Triad Drug Discovery Group meeting. Dr. Arimilli was a good speaker and provided both general background information regarding the metabolism of drugs for the non-medicinal chemists in the room as well as some greater chemical details regarding metabolism to meet the needs of the medicinal chemists in the audience. Some of the key points that Dr. Arimilli discussed were:
- It is good to run pharmacokinetics on the same species that is being used as the efficacy model.
- In order to reduce the attrition rates of drugs one needs to increase the success during the studies evaluating the absorption, distribution, metabolism, and excretion (ADME) of the drug since 40% of drugs fail here.
- There is a lot of species to species liver enzyme variability. So even after a drug is tested in mouse, rat, dog, and monkey to predict how it will interact in humans, it still takes luck!
- He recommended reading “The Discovery of Ezetimibe: A View from Outside the Receptor” by Clader JW in the Journal of Medicinal Chemistry (2004, Vol. 47, No. 1, pp. 1-9) because it shows the struggle in trying to screen drugs.
The Triad Drug Discovery Group meetings are normally the second or third Thursday of the month and meet on the University of North Carolina Greensboro campus at the Sullivan Science Building in room# SCIE 103. The meetings generally follow a similar agenda. Dr. Lakshmi Kotra normally gives a brief statement at the beginning regarding any housekeeping issues. Then he quickly goes around the room and everyone states their name and where they are from/what they do. It is a good way to quickly learn the type of people in the audience. The speaker will then give a 20-30 minute talk followed by questions/group discussion. After the discussion there is normally time to do some networking with the speaker and other members of the audience.
The Triad Drug Discovery Group is a regional exchange group that was formed by Lakshmi Kotra PhD from University of North Carolina Greensboro and Morris Clarke PhD from Winston-Salem State University. The group is now sponsored by the North Carolina Biotechnology Center which enables them to provide some refreshments for the attendees. The group is interested in the fundamental sciences in the path from biological target and/or biologically active compounds to novel drug discovery. This topic enables a broad pool of talks that range from producing the lead compounds to the intellectual property. The groups goal is to engage the scientific community in the Triad area and beyond in regular meetings discussing topics of interest. Ultimately this will expand the knowledge of the individual researchers who usually develop in-depth knowledge in one specific area, but would need a multidisciplinary footing for translational research as well to succeed in developing novel medicines. The discussions are normally on par or higher than a typical graduate student course.
People that are interested in attending or have any other questions regarding the group are encouraged to send Dr. Kotra and/or Dr. Clarke an email. They are extremely helpful and encourage anyone interested to attend.
The next Triad Drug Discovery Group meeting will be April 16, 2009. Dr. Harel Weinstein from Cornell University will be speaking on “Identification of drug targets for synergy-based therapeutics: microarrays to drug design.”