Barry Potter Lectures Flashcards
Are targeted cancer therapies more harmful to our normal cells?
NO
Less harmful as you’re not targeting such a broad aspect, it’s more specific.
Can be combined with patient selection through identifying responding “sub-populations”, this will also make it more effective than traditional therapies
What is targeted therapy?
Blocking the growth of cancer cells by interfering with specific targeted molecules that are needed for carciogenesis and tumour growth.
This is different to eg. Traditional cytotoxic chemotherapy, we simply interfere with rapidly dividing cells.
What is a biological anti cancer drug?
Usually a large (over 45 residue) peptide or protein either isolated from an organism/ cell line
or produced by biotechnological means in a surrogate host!
What are the 7 types of available anti cancer drugs (I.e how are they derived)?
Biological
Natural products
Derived from natural product, but semi synthetically modified
Natural product mimics
Totally synthetic drugs (usually found by screening/ modification of existing agents)
Total synthesis, but pharmacophore from a natural product
Vaccine
What does serendipity actually mean?
It is the accident of finding something good or useful while not specifically searching for it. I.e coming across something by accident.
The discovery of cancer chemotherapy was the serendipitous discovery of the Mustard family of agents
You then go on to apply medicinal chemistry to sulfur mustard gas: lead to agents still used today
Chlormethine Chlorambucil Melphalan Cyclophosphamide Estramustine
Are all examples of what?
Nitrogen mustards Show development (in that order) from mustard gas through molecules with progressively decreasing toxicity to one that attempts to target the oestrogen receptor in tumour cells
What are cisplatin, carboplatin and oxaliplatin all a member of?
The cisplatin family
These were also discovered through serendipity and chemistry
They involved inorganic and analytical chemistry
What features make natural products very specific for particular targets?
Compared to typical synthetic libraries: They have greater chemical complexity They have complex stereochemistry Greater chemical diversity Therefore they are very SPECIFIC They are Hard to produce on a commercial scale
How can semi synthesis be used to help to make natural products commercially if they’re so specific ?
Use a more easily obtained naturally occurring precursor
This semi synthesis is used to make the anti cancer agent Paclitaxel
Start with 10-deacetyl baccatin (this is your naturally occurring precursor which is renewable compared to natural Paclitaxel which is rare!) which you can get from leaves of the English Yew tree.
What is Paclitaxel semi synthesised from?
Baccatin
10-acetyl baccatin
They’re still screening extracts of plants bacteria and fungi for anti cancer agents
Plants are used in traditional Chinese medicine to treat cancer
Indicates there may still be value in ethnopharmacology
How do you screen for anti cancer drug leads?
Screening programmes using cancer cell lines in vitro
