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).

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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).

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