Week 11 Post 1

Week 11 notes
-libraries allow us to sample drug space with meolecular collections
-high throughput screening is our method of quickly testing our molecules
-the drug space is a vast amount of molecules that could be a potentially drug
-a hit had a Ki or a binding activity of binding to the target protein of around 1 micromolar
-once you discover a hit through a htps (high throughout screening) go back and check if it’s pure and not decomposed
-number of hits can be about .1% of the library to 10% of the library
-hits can be selected by Ki value or if you have a molecule you want to outperform
-when looking at a bell curve, the .1% is three std dev from mean
-a library is massive, so even with .1% you have a lot of compounds to search through
-you don’t want to pick the best ones, as some may not show desirable pharmacokinetic properties
Video 2 - Fragment based drug discovery
-the amount of molecules in the drug space is 10^63 molecules
-most hits have 20-25 non hydrogen atoms
-chemist will sometimes narrow the search by only testing molecules with 10-15 non hydrogen atoms
-drugs tend to have a Ki of 10 nanomolar
-hits/leads have about 1 nanomolar
-fragments have 1 millimolar
-goal is to have fragments that bind to specific parts of the drug and then connect them and hopefully it is a drug
-benefits include having a much smaller library, usually only 2,000-5,000 compounds
-nice for new companies and for universities
-problem is connecting the compounds, which becomes a synthetic Chem problem
-then test the connection to see if it fits, if the connection is in the wrong place
Video 3- drug libraries
-if you think about drug space as a game of battleship, there is a lot of non-hits. However there are regions where there are many hits
-the goal of drug discovery is to search trough drug space to find a hit
-modify the structure to increase potently
-hits are found with compound libraries. They are collections of molecules
-in house libraries are a collect of molecules that chemists at a company have made, and the libraries are bigger then longer the company has been at it
-if the target molecule changes, you must retest each molecule to find a hit again
-also can grow with acquisitions
-this can diversify libraries
-there are companies who aren’t drug companies that have a library they sell access to
-many types of this kind of companies

Comments

  1. Ms. DunleyJanuary 17, 2018 at 1:05 PM

    I still am having a hard time with the concept of drug libraries.

    ReplyDelete

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