22 - Lecture 22: Drug Design Monday, August 23, 2010 A...

Info iconThis preview shows pages 1–7. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Lecture 22: Drug Design Monday, August 23, 2010 A large part of the biotech and pharmacological industry is involved in discovering and developing small molecules that ameliorate or cure diseases by interacting with a specific protein target . What does this process involve? Monday, August 23, 2010 Drug discovery: Screening compounds. Identify a target : an enzymatic reaction or cell Develop an in vitro assay : for an enzymatic reaction, create an assay that can measure the effect of a compound on its activity. Screen : Subject the cell (bacteria, mammalian tissue culture) or enzyme to millions of compounds in a library to find those that affect the targeted process (bacterial growth, enzymatic catalysis...) Monday, August 23, 2010 Find lead compounds: From the screen, identify those that act in the desired fashion. Protein target: does compound bind with a K d < 1 mM? Inhibitor: what is K I or K I (competitive or uncompetitive inhibitor) of the compound? For cells: what is the toxic dose? the effective dose? Monday, August 23, 2010 The IC 50 of a compound is the concentration at which the enzyme exhibits 50% maximal activity. This can be determined for an enzyme that exhibits MM kinetics by: v I /v o = (K M + [ S ]) / (K M + [ S ]) and when v I /v o = 0.5 (50% inhibition), [ I ] = [ IC 50 ] = K I (1+ [S]/K M ) Monday, August 23, 2010 A good lead compound is the springboard for its improvement to a more ecient drug. This is done by making thousands to tens of thousands of derivatives of the lead compound, through systematic variation of its chemical structure. Typically, even small changes such as the addition/removal of an amine, hydroxyl, chloro- or benzyl group may have large effects on the...
View Full Document

Page1 / 31

22 - Lecture 22: Drug Design Monday, August 23, 2010 A...

This preview shows document pages 1 - 7. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online