Card Set Information
Med Chem Antivirals Antineoplastics
What do antimitotic agents do?
Inhibit topoisomerase and microtubule formation
How do vinca alkaloids work?
They prevent the formation of microtubules, which prevents the sister chromatids from pulling apart. This causes the cell to go into the cell death pathway because there is "too much" DNA present.
How do taxanes work?
They prevent the deconstruction of microtubules, which leads to the cells becoming clogged up, resulting in the "death pathway".
What is paclitaxel used for?
Breast and Ovarian cancer
What is the MOA for paclitaxel?
Stabilizes the microtubules and inhibits their destruction; leads to the cells 'clogging' and stops the metaphase spindle configuration
Where does paclitaxel come from?
Bark of yew trees
Now semi-synthetically derived
What is Docetaxel used for?
Breast and lung cancer
What is the toxicity for paclitaxel and docetaxel?
What is the MOA for docetaxel?
Same as paclitaxel
What is the MOA for ixabepilone?
Works very similarly to paclitaxel
Apparently more potent than paclitaxel and not as prone to resistance.
Nitrogen is able to form a bond with O
Which indications is ixabepilone approved for?
Advanced breast cancer that is resistant to treatment with an anthracycline and taxanes
Name an epothilone
Where did eribulin come from?
What is the clinical use of eribulin?
Treatment of breast cancer resistant to other therapies
What is the MOA for eribulin?
Triggers apoptosis after prolonged mitotic blockade
What is the MOA for Imatinib (Gleevec)?
Tyrosine kinase inhibitor
Blocks phosphorylation events in signaling
What is the toxicity for gleevec?
Can be taken at home
What is the clinical use for gleevec?
Chronic myelogenous leukemia
GI stromal tumors
What is the MOA for gefitinib?
Blocks phosphorylation catalyzed by epidermal growth factor receptor (EGFR) and some other kinases
Gefitinib originally reported no adverse effects. What is the current AE?
What is the black box warning for nilotinib?
What are the two drug transport resistance mechanisms?
What are the three point mutation and regulation resistance mechanisms?
What is the point mutation resistance mechanism?
What are the two regulation resistance mechanisms?
DNA repair enzymes
Which drugs are important in P-glycoprotein resistance?
What are the trends of P-glycoprotein resistance drugs?
Where are membrane transport resistance mechanisms important?
How do membrane transport mechanisms work?
Nucleosides require certain cotransporters
Modify expression of these transporters to vary the concentration of drugs
How many different membrane transporters are there?
At least 6
What is the resistance mechanism for alkylators and how does it work?
Upregulates in response to alkylators
What is the MOA for methicillin?
Inhibits bacterial cell wall synthesis
What is the MOA for tetracycline?
Binds to bacterial ribosomes
Inhibit protein synthesis
Target 30S subunits are not found in mammalian cells
What is Mylotarg and why is it important?
First clinical example of a drug that targets specific cell types
Withdrawn in 2010 after reports suggested it had no additional benefit and resulted in patient deaths
Provide an example of bacterial drug inactivation
Beta-lactamases - penicillinase derivative that attacks the amide group of a beta lactam and inactivates it; chemical modification
Provide an example of point mutation.
HIV-1 rapid mutation to resist protease inhibitors; occurs on the genome level
Provide an example of regulation resistance
NF-kappaB (which helps resist apoptosis) that is produced by tumor cells in response to drugs
What were the first alkylating agents?
In addition to DNA, alkylating agents might also bind to _____.
Which cell-cycle checkpoint do alkylating agents target?
No specificity for check points
What is the major target for alkylating agents?
N7 portion of guanine (the most nucleophilic nitrogen)
What is a major problem for alkylating agents?
DNA damage can quickly be repaired
Damage may cause secondary carcinomas
How does a bifunctional alkylating agent work?
By cross-linking guanosine nucleotides in DNA strands, preventing them from uncoiling and separating
Which is more efficient at initiating cell death, mono or bi- functional alkylating agents?
Bifunctional alkylating agents
: More effective, cross-link DNA strands
: cause single-strand DNA breaks, more easily repaired
What is the MOA of mechlorethamine?
Cross-links guanine residues; bifunctional
What are the drugs involved in MOPP protocol?
What are the clinical uses for mechlorethamine?
Chronic lymphoctyic leukemia
What is the toxicity of mechlorethamine?
Bone marrow suppression
How is mechlorethamine rapidly inactivated?
By hydrolysis, t1/2 = 15 min
How do you increase the reactivity of a nitrogen in a nitrogen mustard?
Add a EWG to increase acidity
What is the MOA for cyclophosphamide?
Acrolein - byproduct of cyclophosphamide metabolism
Why is carmustine special?
It is very non-polar and can cross the BBB