14th March - Future directions in therapeutics Flashcards
What are the traditional forms of cancer therapy?
Surgery
Radiotherapy
Chemotherapy
Targeted Drugs
Give an example of a cytotoxic drug that targets DNA synthesis
cis-platin
Etoposide
Which cytotoxic drug is on WHOs list of essential medicines?
cis-platin
Give an example of a cytotoxic drug that targets cell division
Vinblastine
What is oncogene addiction?
The dependence of some tumours on a single oncogenic protein for sustaining growth and proliferation
What does Trastuzumab target?
(aka Herceptin)
Targets HER2 in breast cancer
What is personalised medicine?
Use of a biomarker for a target to define subgroups of patients and decide on the best therapeutic strategy
How are molecules chosen for drug development in targeted therapies?
- Find the protein target/pathway that is directly responsible for the disease i.e. understand the molecular basis of the disease
- Find a molecule that is able to abrogate the aberrant behaviour responsible for this disease and develop treatment based on this knowledge
- Perform an activity assay on compounds
What are the different compound libraries used in drug development?
Large compound library
Focused library
Fragment library
Virtual screening
Describe a large compound library
About 100 000 diverse compounds
Mw about 500 Da
Requires an inexpensive high throughput assay
Describe a focused compound library
Hundreds to thousands of compounds that are known to inhibit an enzyme calss
Efficient but lacks novelty
Describe a fragment library
About 1000 compounds
Mw about 200 Da
Efficient coverage of a chemical space
Requires a very sensitive assay
Describe virtual screening
Conformational docking of compounds into the target structure
essentially unlimited compounds
requires a high resolution structure of the target
What drug targets the common Thr315Ile mutation in BCR-ABL?
Ponatinib
What protein fusion is common in NSCLC patients?
EML4-ALK
