Flashcards in Drug Discovery and Development Two Deck (16):
What are some methods for binding detection?
HTS (High Through Put Screening)
vHTS (virtual " ")
What is HTS?
The use of robotics to screen molecules for an effect against a target protein
Whats needed for HTS?
- Large library of compounds
- Any hits require validation of chemical structure and activity
- Hits from the same chemical family can form a lead series
What is vHTS?
Computer based program
Screens using two methods:
- Receptor based (3D)
- Ligand Based (3D and 2D)
When performing HTS how do you choose a library to screen?
- Based on relationship of known active molecules
What is pharmacophore perception?
The spatial arrangement of molecular features essential for biological activity
How are new ligands discovered using protein structure?
What is molecular docking?
Molecular docking predicts the binding modes of small organic molecules based on optimizing the complementary between physicochemical properties of the target site and the ligand
How is molecular docking useful?
screens large samples and scores them
How is molecular docking scored?
Fitness function scores the poses. (based on interactions)
Whats assumed in molecular docking?
The ligand is treated as flexible while the protein is considered rigid
Describe the pathway from discovery to preclinical trials
Hit to lead
What are three key features of hit discovery?
- Cluster compounds
- Dose response
- Chemical synthesis
A molecule active in the drug target assay (changes the phenotype)
What are five key features of hit to lead?
- Drug metabolism
(improved potency, selectivity, DMPK properties, basically refining the drug)
What are three key features of lead optomization?
- Minimize toxicity
- Improve bioavailability
- Monitoring in-vivo efficacy
( Using analogues)