parang m phase agents

List m phase specific agents

taxanes vina alkaloids, epothilone ixabepilone

MOA of vinca alkaloids

inhibit polymerization by binding to two hetterodimers on Beta subunit and promoting incorrect formation of tubulin = inhibit polymerization

MOA of taxanes

inhibit depolymerization by forming asters to stabilize tubule

Where is the binding site of taxanes

beta tubulin

Where is the binding site of epothilone

bet tubulin

Where is the binding site of lauilmalide

alpha tubulin

Vinca binding site

between alpha and beta heterodimers

MOA of epothilone

inhibit depolymerization

What components are in the SAR of taxanes

1. C12 isoserine 2. Benzoyl ester C2 3. Acetyl C4 4. Intact oxetane ring

What is the difference between the taxane drugs

paclitaxel has 3 benzene rings, docetaxel has ester and OH in center ring, cabazitaxel has ester and ether

How is paclitaxel formulated

solution with alcohol and kolliphor (hypersensitivity), albumin nanoparticle

How can you help with reactions for paclitaxel

antihistamine + corticosteroid

What is abraxane and indication

albumin nanoparticle = breast cancer

Why is paclitaxel administered with capecitabine

paclitaxel upregulates thymidine phosphorylase to increase activation of capecitabine

Docetaxel indication and formulation

NOT ovarian cancer, and formulated with tween 80 instead of castor oil

Cabazitaxel vs other taxanes

cabazitaxel has lower P-gp affinity and is used for drug resistant prostate cancers to taxanes

Issue with taxanes

low water solubility since it is hydrophobic, high P-pg efflux (except cabazitaxel)

Why can epothilones overcome resistance to taxanes

different binding site, enhanced water solubility and lack of P-gp affinity

Difference between the vinca alkaloids

vincristine: has aldehyde near benzene, vinblastine: has amine near benzene and two carbon spacer between top nitrogen heterocycle, vinorelbine has methyl and double bond vincristine has highest binding affinity > vinorelbine > vinblastine

SAR of vinca alkaloid

catharanthine and vindoline subunits

How does vinca alkaloid resistance occur

P-pg efflux

Marqibo components

liposomal (sphingomylein and cholesterol) formulation of vincristine