Aw Flashcards
How to increase profits 5
How can a company increase profit?
- Reduce the time it takes to get on the market.
- A better success rate of drugs going into trials.
- Safety profile of the drug, more specific with less side effects speeds up the approval process.
- Toxicity, lower this to reduce failure in clinical stage.
Av time to market
Useful patent life
Patent life
Time to market - 14y
Patent life - 17y
5 are useful
One in how many compounds makes it to market?
10000
Tactics for making more specialised drugs and ensuring target is correct
Biopharm genomics and protein omits
Understanding the link between diseases, genetic makeup and expression of proteins
HTP
Screening up to 100000/day for activity against a protein target
Screening perhaps millions of compounds in a corporate collection to see if any show activity against a certain disease protein
Virtual screening
Uses a PC to predict activity so you don’t need to make compound
Combinatorial chem
Rapidly producing vast numbers of compounds
Molecular modelling
Computer models to improve activity, may be part of virtual screening
Allows visualisation of docking
What is replacing animal testing and why? 2
In vitro and on silico testing (computer and tissue)
Faster, fewer ethical issues
Three properties a drug needs
Chemical stability (shelf life)
Solubility (access to tissue)
pKa (soluble at ap pH)
Biological properties a drug needs 6
Biodistribution (high conc at site of action)
Metabolism (where and into what? metabolites toxic before excretion?)
Half-life (correct form long enough for effect)
Potency (impacts dosing regime, higher doses = side-effects)
Specificity (ideally highly active against one protein)
Toxicity (Nein, danke)
bioisosteres
Structurally distinct molecular fragments
Framework is structural units that are 2
Metabolically inert and conformationallay restrained
Why is framework usually hydrocarbon?
Not soluble in water but very soluble in other shit ( such as other hydrocarbons)
Genomics defien
Genomics is fast-forwarding our understanding of how DNA, genes, proteins and protein function are related, in both normal and disease conditions
Hops for genomics
Identify new targets and personalise therapies
Gene chips
Allow is to look for changes in protein expression in different people/condition
And see if presence of drug changes that expression
Biopharmacueticals
Drugs based on proteins, peptides or natural products instead of small molecules (chemistry)
Natural proteins already ‘designed’ to interact with receptors - cuts time to market in half
Hts how many of the screened will have acitivty?
Maybe thousands in a collection of millions, chemist must select 2-3 to proceed
Informatics implications 3
• Need to be able to store chemical structure and biological data for millions of datapoints – Computational representation of 2D structure
• Need to be able to organize thousands of active compounds into meaningful groups – Group similar structures together and relate to activity
• Need to learn as much information as possible from the data (data mining) – Apply statistical methods to the structures and related information
Comb chem
By combining molecular “building blocks”, we can create very large numbers of different molecules very quickly.
• Usually involves a “scaffold” molecule, and sets of compounds which can be reacted with the scaffold to place different structures on “attachment points
Which comb chem what later process is essential
HTS to test them all
Comb chem issues
- Which R-groups to choose
- Which libraries to make – “Fill out” existing compound collection? – Targeted to a particular protein? – As many compounds as possible?
• Computational profiling of libraries can help – “Virtual libraries” can be assessed on computer
Vapour diffuse method
Hanging drop of protein solution will crystallize as water diffuses into half strength solution below
