Drug Discovery Flashcards
Target (Protein)
The pathway (gene to protein to cell interaction) that results in some form of condition with clinical relevance. For example: the Renin-Angiotensin-Aldosterone-System
Screening Assay
A cost effective method of screening multiple compounds to determine their compatibility with the Target.
High Throughput Screening
The high volume testing of multiple varied compounds. These compounds could have been organic or synthetic in origin. Automated process.
Hit
A compound identified through High Output Screening that succeeds in interacting with the Target.
What are the four types of Bioassays?
Whole organism, mammalian cell cultures, purified enzymes or receptors, engineered microorganisms
Lead Compound
The most successful of the Hits in the realm of toxicology and pharmacology
Lead Optimization
Altering the Lead compound to maximize efficacy by modifying the binding of said drug
Natural Products
A processed crude mixture of some material found in nature such that each of its many components are isolated for testing.
Synthetic Compound Collections
Large collections of synthetically created compounds. They have limited structure options.
Combinational Libraries
Large quantities of rapidly generated compounds made from chemical recombination. Libraries tailored to specific structures are the most successful of this concept.
Virtual Libraries
A digital database of thousands of molecules that can be screens for molecular compatibility.
Eutomer
A stereoisomer with the highest receptor afinity
Distomer
A stereoisomer with the lowest receptor afinity
Pharmacophore
The three dimensional arrangement of essential functional groups that cause a biological response. This is the minimum requirement for activity.
Homologation
Adding similar constituents to a pharmacophore. Often varying lengths of one carbon structure.
Chain Branching
Changing pharmacophores with different branching additions. Nitrogen and Carbon can both provide branches in this manner.
Ring Transformation
Replacing structures of a pharmacophore until they form a ring structure. This requires two available locations for modification.
Bioisostere (Classic)
Molecules or ions with the same number of atoms or the same numbers and arrangements of valence electrons.
Bioisostere (Non-classical)
Groups of atoms with similar chemical or physical properties.
QSAR
Quantitative Structure Activity Relationships. The mathematical models that predict the viability between a drug and a receptor.
Log P
The measure of Lipophilicy which is relevant for QSAR. It is the ratio of the drug’s concentration in Octanol and concentration in Water.
Water soluble (Log P)
A Log P value of 0.5 or less indicates it is water soluble.
Lipinski’s Rule of Five
Four broad rules that indicate a good drug molecule: 1. MW
