MDT - Mitotic spindle poisons Flashcards
What is a spindle poison?
a spindle toxin, is a poison that disrupts cell division by affecting the protein threads that connect the centromere regions of chromosomes, known as spindles. Spindle poisons effectively cease the production of new cells by interrupting the mitosis phase of cell division at the spindle assembly checkpoint (SAC).
What is the mitotic spindle?
The mitotic spindle is composed of microtubules (polymerized tubulin) that aid, along with regulatory proteins; each other in the activity of appropriately segregating replicated chromosomes.
What are the two specific families of antimitotic agents?
Vinca alkaloids
Taxanes.
How do the vinca alkaloids work?
Inhibit the polymerisation of tubulin into microtubules, resulting in G2/M arrest in the cell cycle and eventually cell death.
How do the taxanes work?
They stabilise microtubules against depolymerisation.
What is vinblastine?
A vinca alkaloid.
It binds to the + end of the microtubules, capping it and preventing new tubule dimers from adding on.
_____ ______ bind strongly to individual tubulin dimers, causing conformational change and preventing binding to microtubules.
Vinca alkaloids bind strongly to individual tubulin dimers, causing conformational change and preventing binding to microtubules
Individual complexes of _____ _______ and tubulin dimers condense into paracrystalline aggregates.
Individual complexes of vinca alkaloid and tubulin dimers condense into paracrystalline aggregates
How does Le Chateliers Principle apply to the action of vinca alkaloids such as _________?
Vinblastine.
Microtubules shrink.
How do Taxols work?
Taxols bind to taxol-binding sites on the inside surface of the microtubule, preventing disassembly.
Inappropriate microtubules remain.
Concentration of free tubulin dimers decreases as more and more microtubules are made which cannot subsequently be broken down.
The low concentrations of free tubulin dimers means that new microtubules cannot be assembled.
What are two examples of taxols?
Docetaxel.
Paclitaxel.
How do Colchicine-like drugs work?
Bind to colchicine binding sites on the B-tubulin subunits, disfavouring assembly of protofilaments.
ALSO
Colchicine bound at colchicine binding sites on B-tubulin in microtubules disfavours disassembly of inappropriate microtubules.
How do vinca alkaloids prevent tubulin dimers from binding to microtubules?
Vinblastine binds to + end of microtubule, capping it and preventing new tubulin dimers from adding.
Vinca alkaloids bind strongly to individual tubulin dimers, causing conformational change and preventing binding to microtubules.
Docetaxel and Paclitaxel are examples of
Taxols
Drug class that causes innappropriate microtubules to remain and concentration of free tubulin dimers to decrease.
Taxols
