Lead Identification and Optimization Flashcards
(40 cards)
Who is known as “The Father of Microbiology”?
Anton van Leeuwenhoek
He was the first person to identify bacteria via microscopy.
What did Louis Pasteur do?
He developed the link between bacteria and disease.
What did Koch do?
He identified the micro-organisms for anthrax, TB, cholera, and typhoid.
What did Lister do?
He helped create the “germ theory of disease”. He used carbolic soap to prevent infections during his surgeries. He was a pioneer of antiseptic surgery.
What did Ehrlich do?
He coined chemotherapy.
He used synthetic chemicals to try and cure disease.
Who had the proponent of the “Magic Bullet”?
Paul Ehrlich. He aimed to use chemicals to treat disease.
What was the first fully synthetic drug?
Salvarsan. It contained 605 arsenic containing compounds. It wasn’t good against bacteria, but was good against sleeping sickness and syphilis.
What are 5 drug targets for small molecules?
Enzyme Receptor Nucleic Acid Ion Channels Transporters
How can a drug be validated?
It must be shown to play a critical role in the disease process.
What are 3 strategies for target validation?
Gene Knockout
RNA interference
Small molecules
In order to make a new drug for a disease target what must you prove compared to the existing therapy?
You must prove the new agent has a statistically proven clear advantage, not just clinically effective.
A new dosage form, less frequent dosing, new target, increased selectivity, etc…
What is a lead compound?
A compound with desired biological activity. This can be characterized and modified to produce another molecule with a better profile of wanted properties and less unwanted side effects.
What does the start of a drug discovery project rely on?
The “make and test” cycle.
How does Ibrance and Letrozole work to help in breast cancer?
Ibrance inhibits CDK 4 and CDK6 from telling the cell to proliferate
Letrozole decreases the production of estrogen, which prevents it from activating CDK 4 and 6.
What are some sources of lead compounds?
Chance Observations Natural products from folk remedies Random screening Substrate Analogues Structure-based design
What is the largest group of recreationally used drugs in the world?
Flunitrazepam
In 2008, the FDA approved Thalidomide for the treatment of what in combination with dexamethasone?
Multiple myeloma.
What is the primary target of thalidomide?
CRBN (Cereblon)
The optimization of what lead to the development of diuretics, such as chlorothiazide?
Sulphanilamide
General natural product screening is widely used as a method of finding what?
Lead compounds
About __% of drugs in clinical use originate from natural products or their derivaties.
45%
What is used to treat River Blindness and Lymphatic Filariasis?
Ivermectin (anti-parasite), which originated from Avermectin.
What is the agent that Tu developed into an anti-malarial drug?
Artemisinin
What are 3 advantages of natural product screening?
Molecules are structurally diverse
Much precedence as a source of lead compounds: Pharmacologically pre-validated.
