Lectuer 6 Flashcards
What is the magic bullet? What did it contribute to?
Salvarsan by Paul ehrlich
—seletive affinity
What is methylene blue?
Used to stain acidic parts of cells—-> nucleus, bacteria & blood tissue
When is a drug efficacious?
What is bioavailability?
If it distributes to its target
—amount of drug that makes it to the plasma
What does the portal vein have to do with bioavailability?
Goes into GI—>into portal vein—> to liver, where most is metabolized
What is the brain good at keeping out?
What is the main efflux pump of the BBB?
Xenobiotics
P glycoprotein
What activates & inactivates the P glycoprotein BBB pump?
Drug alone
Drug + amitriptyline (improves drug delivery across BBB)
What does P glycoprotein do?
What expresses PGP?
Where is it highly expressed?
Highly expressed ATP dependent efflux pump===> pumps xenobiotics out of cells
CACO2
Intestinal epithelium & BBB
What does Lipiński rules of 5 measures?
What are 3 of them?
Solubility and drug permeability
LogP<5, is hydrophilic (measures lipophilicity)
MW<500
HBD<5, HBA<10
Examples of drugs that follow Ro5?
Examples of those r that don’t follow Ro5?
Januvia & Getfitinib ( less lipophilic & low MW)
Rapamycin & navitoclax
What is polar surface area?
What does it measure?
What does it depend on?
Sum of surface areas of polar atoms (NOS) & their bonded hydrogens
Ability to form H bonds
Depends on 3D conformation—-want to be lower than 140A
For polar sufurace area, want lower than _____ to _____ and lower than ____ to cross the _____
—140A to be permeable
—90A to cross BBB
What is the correlation between polar surface area and percent absorption ?
—negative correlation
— as polar surface areas increases, percent absorption decreases
What does ligand and structure based design use?
Chemical similarity, pharmacophore, QSAR
Molecular docking & scoring
What is chemoinformatics?
Computer sciences to manage and analyze & visualize chemical information
Example of a type of chemoinformatics?
SMILES——Simplified molecular input line entry system
One way to get the molecule into the computer
What is featurization?
Uses vectors to predict properties or behaviors of compounds
What is property representation ?
Show HBA , HBD, cations, anions, hydrophobicity & aromatics
What is phas 1 and phase 2 drug discovery?
Drug discover (1)—> target mod, validation, lead identify, lead optimization
Development (2)—> preclinical, clinical, approval
