Drug Discovery Flashcards
Define NME in the context of pharmaceutical industry
New Molecular Entity- the name for a new drug candidate. This encompases a NCE (new chemical entity) and NBE (new biological entity)
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Name some emerging trends in the market and their implications
Patients are becoming more informed
Patients are picking up a bigger share of the bill
Demand for personalized medicine is increasing
Patients want cures, not treatments
Emerging markets are becoming more important
Name some emerging trends in health and healthcare
The burden and bill for chronic disease is soaring
Healthcare payers are establishing treatment protocols
Pay-for-performance is on the rise
The boundaries between different forms of care are blurring
Financial constraints on payers are increasing
Name some scientific and technological trends in drug discovery
R&D is becoming more virtualized
The research base is shifting to Asia
Remote monitoring is improving rapidly
AI / machine learning integration (my own addition)
What percentage of drugs dispensed in the US are for generic drugs?
90% (as of a 2021 detailed in a report from the FDA)
What are the implications of the market trends, health and healthcare trends, and technology trends?
Outcomes data will drive healthcare policy (e.g. cardiovascular seeking fewer cardiac events and not just reduction of a biomarker)
Prevention will gain a higher healthcare profile
Pharma and healthcare value chains will become much more intertwined
* Pharma will have to collaborate with numerous service providers to deliver packages of care
Pharma will need to offer “medicine-plus” packages of care
Pharma will be paid for outcomes, not products
R&D will need to go beyond the lab
* (incorporate diagnostics, treatments, outcomes, monitoring)
* work with technology vendors
Gene knock-outs only effect phenotype in what percentager of cases? Why?
Gene knock-outs only effect phenotype in 10-20% of cases because of:
* Redundant functions
* Alternative network routes
* Robustness of interaction networks
What percent of biologically active compounds bind to more than one target?
What does this mean for drug discovery?
35% of drugs bind to more than one target
This means that a one-drug, one-target, one-disease approach is extremely faulty. Your off-target effects will produce side-effects, may be the reason why your drug fails, etc. Here is a photo of various drugs affecting human kinases
Define polypharmacology
Using one or multiple drugs that bind to multiple targets for a collective effect. AKA Dirty Drugs
An example from class is finding a “promiscuous” drug that binds a whole bunch of targets in tuberculosis. The odds that TB can become drug resistant to a promiscuous drug is low because multiple things would have to evolve at once. The tricky part is overlaying the human proteome and trying to MINIMIZE the number of bindings to the human.
Network Pharmacology
Measuring the effect on the whole biological network
Systems Pharmacology
What percentage of drugs target the cell surface? G-protein coupled receptors? What percentage of prescriptions does that account for?
- 60% are on the cell surface (old data from like 2007)
- 33% of all prescriptions Drugs target G-protein coupled receptors (12% of drugs) (newer data from 2017)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314433/
Erooms Law and possible reasons
The observation that drug discovery is becoming slower and more expensive over time
Possible reasons:
* The “better than the Beatles” problem
* The “cautious regulator” problem
* The “throw money at it” tendency
* The “basic research-brute force” bias
Define morbidity
The condition of suffering.
