Drug Discovery

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Case 6
Simeon Crane
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Simeon Crane
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Pregunta Respuesta
What are the 7 steps in the modern drug discovery process? - Target identification - Target validation - Lead discovery - Lead optimisation - Pharmacological and toxicological profiling - Formulation development - Marketing authorisation
Name 3 methods for identifying drug targets DNA microarrays Proteomics RNA knockdown
What are isosteres? Molecules or ions of similar size containing the same number of atoms and valence electrons
Name 2 tests that are used to detect genotoxicity of a new drug - Bacterial reverse mutation (Ames) test - COMET assay
What is meant by lead discovery in drug discovery process? The process of identifying active new chemical entities, which by subsequent modification may be transformed into a clinically useful drug
What is the Easson-Stedman Hypothesis? If two enantiomers demonstrate different activities at the same target, then three sites on the molecule must be involved in the interaction between drug and target
What is combinatorial synthesis? A process used to prepare large sets of organic compounds by combining sets of building blocks
Name 4 drug related factors that affect the transport of drugs across biological membranes - Concentration - RMM - Lipophilicity - Chemical structure and functional groups
According to Lipinkski's rule of five, what 4 factors affect drug absorption? - Number of H-bond acceptors - Number of H-bond donors - Log P - Molecular Weight
What is the most commonly encountered reason for using pro-drugs for the delivery of therapeutic agents? To reduce the toxicity of a drug
What does QSAR stand for? Quantitative structure-activity relationships
What is a prodrug? A biologically inactive molecule that is metabolised to produce the active drug
Name 4 types of drug degradation - Hydrolysis - Oxidation/Reduction - Photolysis - Trace metal catalysis
What 5 factors will the particle size of a drug affect? - Solubility and dissolution rate - Content uniformity in the final dosage form - Flow characteristics - Sedimentation rate - Bioavailability
What are the 3 basic rules of formulation design? - Select excipients based on formulation type - Determine excipient compatibility - Use minimal number of excipients
What 3 factors determine if a drug should be formulated as a SVP or a LVP? - Route of administration - Onset/duration of action - Concentration of drug in the product
What are the 8 components of a Target Product Profile? - Business plan - Drug Discovery - Drug product development - Pre-clinical investigations - Phase 1 clinical trial - Phase 2 clinical trial - Exit strategy - IND/NDA application
What is Pharmacoeconomics? The comparison of VALUE of one drug product or drug therapy over one that is already available to the patient
What two properties do class 2 drugs in the biopharmaceutical classification system have? Low solubility High permeability
What characteristics of a drug has the greatest effect on the rate of passage through a biological membrane via passive diffusion? Polarity of the drug molecule
What is the role of propylene glycol in a transdermal formulation? Penetration enhancer
A drug molecule has high aqueous solubility and low permeability. What class in the biopharmaceutical classification system would it belong to? Class 3
What is a pharmacophore? A part of a molecule structure that is responsible for a particular biological or pharmacological interaction that it undergoes
What is the most commonly used measurement of lipophilicity? LogP
What is the most common type of drug target? Enzymes
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