Chatting with Christopher Lipinski at Drug Discovery & Development Week

Some ten years ago, I first “met” the Lipinski rules in a software project.  That was my last direct “hands-on” encounter with chemistry.  At Accelrys I am the senior product manager for the Biosciences and Analytics Collections for Pipeline Pilot.  Think genomics, proteomics, sequencing, and ontologies and not chemistry!  This week I was at the DDDW show in Boston – don’t think “booth babe”.

The conference was not as busy this year as it had been in the past and it was the afternoon of the last day.  A distinguished gentleman walked up to our booth wearing a name tag of “Christopher A. Lipinski,” happy to see a fellow booth dweller.   Half in jest I asked if he might be the man with 5 rules.  Turns out he was and, boy, I was in for an intellectual treat.   That Lipinski filter came to life in a new way over the next hour or so.  I was spell bound by Dr. Lipinski’s breadth of knowledge, passion for science, and his out of the box thinking.  What I didn’t anticipate were his insights into the importance of chemistry for the biomarker and translational research space.

He was saying some really awesome things so I started writing them down.    It was hard to focus on note taking because Dr. Lipinski is an excellent speaker and very animated.  Below are a few items that I am willing to share in no particular order:

• Translational research must have good chemistry married to good biology.
• Your company (Accelrys) combines chemistry and biology in one software application.  If biologists are using your software to look at high throughput screening (assay) data that has associated chemical structures, they could better filter out results for poor compounds.
• When faced with people problems (like chemistry—biology conflicts) versus technical problems—the people problems are always much more difficult to solve.
• The people side is the most important.
• NIH is making good strides in the dialog between chemists and biologists.
• As soon as the biologist has an assay for a small molecule they should probe/stress test the assay with compounds known historically to cause assay problems.
• In software for the (bench) biologist – it needs to be dead easy.  Too many peer-reviewed publications have great biology but rotten chemistry.
• Biologically active compounds are tightly clustered in chemical space.  It is always best to look for new activity in areas of chemical space where you previously found activity.
• It takes 10 years to “mature” a medicinal chemist.  He then becomes an expert in pattern recognition even if he can’t articulate why certain structures look better than others
• Areas of interest
  • Stem cell (non-embryonic source)  derived screening application
  • Many previously proprietary databases are now in the public domain  (See PMID:  17897036).  These provide a great starting point for the discovery of drugs for rare diseases.

Dr Lipinski’s long and prestigious career in medicinal chemistry, assay development, computational chemistry, and now in consulting, lecturing, and as an expert witness does not look anything like retirement.  That is good news for me.

Dr. Lipinski is shown here with his rapt audience.

Note: Lipinski’s total number of rules actually equals 4.  His rules are known as the “Rule of Five” because each of them incorporates the number 5 in some way.  For all you literalists out there, “5 Rules” should be interpreted in this way.