Cognitive skills
1. Analyse and interpret data gathered through computational biology approaches
2. Demonstrate independent thinking, analytical and problem-solving skills
3. Effective use of literature to support explanations and interpretations
Other skills
1. Ability to reflect on learning
2. Effective written communication, with appropriate referencing of the literatu
Data Analysis:
You will be required to assess the safety pharmacology profile of two drug candidates whose names will be revealed on the day of the coursework release.
The pharmacokinetics predictions indicated that the Cmax of the drugs in the blood of patients will be ??? nM for Drug 1 and ??? nM for Drug 2.
From the data generated in the computational pharmacology lab practical:
• Plot target specific IC50 data (e.g. using a scatter plot)
• Use the knowledge of the two Cmax values to identify the sub-set of targets that are likely to be modulated by each drug at concentrations = or < the Cmax
• Considering the two sub-sets of targets:
– Identify the primary target
– Indicate the secondary pharmacology targets
• Rank the sub-set of targets and their IC50 values from the lowest to the highest and present the two sets of data using an appropriate approach (e.g. table or heat map or others).
Problem Solving:
• Evaluate the targets that are likely to be modulated at drug concentrations = or < the Cmax, identify potential safety pharmacology red flags (i.e. targets associated with adverse drug reactions), and predict which of the two compounds is the safer one.
Coursework Submission (MAX 1000 words excluding figure legends):
Prepare a report with the following content
• Outline in brief the main aim of safety pharmacology, and the differences between safety predictions driven by in vitro mechanistic profiling vs in vivo toxicity pre-clinical testing (e.g. describe strengths and limitations of each approach).
• Present the data from the analysis, appropriately labelled with descriptive legends and some descriptive text.
• The modulation of some drug targets is highly predictive of clinical toxicity. Using the safety pharmacology concepts taught in the lectures, discuss why one compound will likely be safer than the other. Support your prediction using published literature on the two drugs.
