Comprehensive Exam

This is the memo for the exam, that I will send you on the Saturday, the 11th July, and I need the answer back within 8 hours. Please read through the instructions and I will send you some of the references that you need to go through and get prepared;

Prodrugs: Design Principles and Disease-Specific Mechanisms
Prodrugs are compounds that are not active themselves, but are designed to become pharmacologically active under certain physiological conditions. An example of prodrug is antibody-drug conjugates (ADCs); typically, their payloads (e.g., small molecule toxic agents) are released only after internalization into the cell.
The exam will focus on several critical aspects of prodrugs:
1. Key design principles, such as various activation mechanisms and their corresponding chemistry (i.e., specific functional groups (triggers and linkers), and their transformations).
Note A: the exam focuses on the design principles, so do not include peripheral information, such as their synthesis, analysis and disease burden.
Note B: activation by exogenous stimuli, such as light and radiation, should be excluded.
2. Disease-specific mechanisms of activation. Each specific activation mechanism needs to be supported by experimental evidences; in other words, sufficient activation levels or pharmacological differences have been observed between disease and normal cells.
Note A: the more the better, particularly distinct mechanisms. Multiple disease can be included.
Note B: Exclude aspects that are not directly involve prodrug activation, such as selective targeting (e.g., cancer-specific antigen for antibody binding) or mode of action of the activated drug (e.g., DNA alkylation).

3. For each activation mechanism, provide critical evaluation of both the pros and cons, particularly in clinical setting. Provide full citations of relavent references, including papers and web resources. If a specific design has been used in drugs that have been approved or in human clinical trials, please provide the details, such as drug names and clinical trail identifiers (NCT numbers).