Lecture 6 Failing Modern Drug Discovery

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21 Apr 2012
Lecture 6 PHC320 Failing Modern Drug Discovery
Failing modern drug discovery
$$$ invested in government and academic, biotech and pharma
60 approved drugs/year
40-45 “re-worked” existing drugs
15-20 NCEs
Preclinical science ~3-5 years
Very little compounds entering clinic are approved.
Most compounds fail for reasons that are unpredictable with our current scientific
With growing economic pressure, we have two choices:
1. Stop developing new drugs
2. Increase productivity
Drugs are needed for unmet medical needs
Ways to increase productivity
1. Stick to “druggable targets” (decreased risk)
Proteins are able to bind drugs that inhibit their adctivity
Portion of genome that is druggable based on studying properties of
approved drugs
Most targets are Rhodopsin=like GPCRs
“druggability” based on what proteins have been successfully targeted and
,must be amenable to HTS
2. New Targets
Currently, drugs can only recognize ~500 molecular targets. Choose validated target
Currently marketed drugs, literature, etc.
This explains the small diversity of targets.
Targets must be successful
Go after individual or family
“good” candidates not always druggable
genomic data “thinly validated” targets
3. Fail Drugs Fast
99% attrition
poor target
intractable chemistry
Animal model stage
predictive for efficacy and toxicity
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