Name the pro-apoptotic and anti-apoptotic BCL2 proteins involved in mitochondrial apoptosis signaling.
• Pro-apoptotic BCL2
proteins – BAD, BID, BAX, BIM
• Anti-apoptotic BCL2 proteins – BCL2,
This pro-angiogenic factor diffuses into nearby tissues and activates receptors on the endothelial cells of pre-existing blood vessels.
DNA Crosslinking agents.
hydrazines and triazines ( do not form crosslinking)
How to identify platinum compounds.
Code reading agents
classes of antimetaolites
Purine analog (6-mercaptopurine)
Pyrimidine Analog (5-FU)
How could cancer be cured by 2015?
•Screening for early detection of malignancies
•Three potential therapeutic strategies to
with selective protection of normal cells
•Change of lifestyle
Why target DNA?
DNA sequence information is pivotal to transcription, replication and recombination. DNA structure is dependent upon intracellular conditions such as ion concentration and the presence of proteins that may bind to DNA to facilitate the interconversion between different
forms and to stabilize specific secondary structures
2.High rate of proliferation of cancer cells
3.Well defined structures
4.Enough complexity to achieve selectivity/specificity
6 Classes of DNA Interactive Agents
1. DNA-DNA crosslinkers
2. DNA intercalators
3.Double stranded break
4. code reading
5. protein-DNA complex
6. Agents which react with secondary DNA structures, such as guanine tetrad (no drug for this class)
4 different forms of cisplatine-DNA adducts
DNA protein crosslinking
Mechanisms of resistance to Cisplatin
decrease the effective concentration in the cell by:
1. Reduction of intracellular drug accumulation (increasing deactivation of Cisplatin by Glutithione or hydrolysis and/or efflux increase
2. increased inactivation by thiol-containing molecules (see above)
3. increase of DNA damage repair
4. increase tolerance
Distinguishing characteristic of DNA intercalator molecules
must be flat
usually aromatic system
Two types of tubulin-binding agents
Polymerization inhibitors – block addition of dimers to growing + end, continue to dissociate from – end
Depolymerization inhibitors – block the dissociation and promote and stabilize the formation of microtubules