We meet in Branford, CT, about once every 4-6 weeks and topics discussed range from physical sciences, to life sciences and social sciences. A knowledge of the topic being discussed is not required, nor is there any membership requirement or age restriction. Perhaps the only requirement is curiosity and a thirst for knowledge! Science and technology are integral to every aspect of life - history, geography, humanities, music - everything.
Now for a piece of excellent news for Tilde Cafe: as of January 23, 2009 you can find a link to us on the science cafes website maintained by WGBH Educational Foundation - WGBH is the public television station out of Boston, and produces NOVA among many other fantastic shows. Tilde Cafe is the only listed science cafe in CT, and the only one between NYC and Boston!
As of July 2014, the IRS has recognized Tilde Cafe as a 501(c)(3) organization. Gifts are deductible to the full extent allowable under IRS regulations.
© 2009 Deepti Pradhan and Tilde Cafe
May 16, 2015
The answer is >>>42
For those who are familiar with the Douglas Adams Hitchhiker series, 42 is the Answer to the Ultimate Question of Life, the Universe, and Everything. But the answer to the question of how much does it cost to create a new drug with the best medicinal chemists working at the problem, is closer to 800 million. Dollars.
Almost a year after our last discussion led by Dr. Daniel Broom relating to pharmacology, Dr. Kevin Currie talked about the complicated yet exciting processes involved in coming up with a new drug. The path to creating a successful drug is littered with failures, red herrings and PAINS (Pan-Assay Interference compoundS - promiscuous molecules). Which is why Structure-Activity Relationship (SAR) studies are at the heart of drug discovery and drug design, and medicinal chemists are critical to this process. SAR studies strive to achieve a balance between an ideal structure of a molecule and the biological effect of that molecule, so that PAINS can be minimized. Typically, the chances of success in drug discovery are about 1-2 % before going to clinical trials, and it can take up to 6-8 years before a drug is available for clinical trials. The entire process from start to approval and access of the drug to patients, has a success rate of 0.1-0.2%. With these low rates, collaboration is key to the process and medicinal chemists work in partnership with computational chemists, computational biologists, x-ray crystallographers, and other specialists, to increase success and reduce the number of PAINS.
The science of drug discovery and medicinal chemistry is complicated by the fact that biological systems are complex. Despite information on the human genome being publicly available, drug discovery for specific diseases continues to be an extremely difficult and expensive process. The human genome is not a linear beast - products of the genome interact with each other in multiple pathways, not all of which have been characterized. Consequently, it is not uncommon to find that what at first, second, and even nth glance appears to be a perfect drug, must be rejected in clinical trials because of unpredicted and undesirable outcomes.
But the issues faced by a medicinal chemist much earlier in the process of drug discovery are what can be both financially demanding and intellectually challenging to surmount. The medicinal chemist is unique in the drug discovery process because chemistry is a science which endows its practitioner the ability to synthesize molecules to order, as long as the laws of physics are obeyed! After an initial understanding of the region to be focused on in a target protein, a medicinal chemist gets to work synthesizing molecules that would fit into that region. Using computer graphics, in some cases it is possible to visualize how the synthesized molecule would align along the target protein, and based on these results medicinal chemists then modify the synthesized molecule further to reach optimal alignments. Other challenges in the discovery of oral drugs include how to package the synthesized molecule so that it can withstand the acidic environment in the stomach and still not lose its structural and chemical integrity, and then make its way through the digestive tract and finally out into the blood stream from where it must pass muster through the vigilant liver, before it is let loose to roam the body and find its target protein! How's that for multiple challenges to a small molecule that came into existence thanks to the assiduous efforts of a team of medicinal chemists and their collaborators?
In general, the likelihood of a molecule becoming a successful oral drug is encapsulated in the Rule of 5 - criteria that include the minimum number of certain types of chemical bonds and atoms in a molecule. However, as with all rules, there are exceptions such as in the blockbuster drug Lipitor. Even so, using these rules as a rough guideline can make the drug discovery process slightly more efficient and narrow down the possibility of PAINS and red herrings. On the bright side, drugs that don't make it to patients despite all the efforts and dollars invested, can be screened and sometimes re-purposed for another disease. As discussed in a cafe led by Dr. Zeldis, the re-purposing process is faster, because the molecules have overcome initial tests for safety.
Thanks, Kevin, for being our guide on a lovely spring afternoon - even if the answer is >>>>>42!
The cartoon below is from the brilliant cartoonist Roz Chast who will be in New Haven next month - http://artidea.org/event/2015/1865 - like Tilde Cafe discussions, it's going to be a free event!
Visit http://www.youtube.com/user/tildecafe for all cafe videos