Medicinal Chemistry

1. Biological Evaluation of Drug Candidates
   1. In vitro testing
      1. Definition and significance of in vitro testing
      2. Cell-based assays
         1. Types of cell lines used
         2. Proliferation assays
         3. Cytotoxicity assays
         4. Reporter gene assays
      3. Biochemical assays
         1. Enzyme inhibition assays
         2. Receptor binding assays
         3. Signal transduction assessments
      4. Organoid and tissue culture models
         1. Utilization in drug candidate evaluation
         2. Advantages over traditional cell cultures
      5. High-throughput screening (HTS) in vitro assays
         1. Miniaturization techniques
         2. Automation in assay processes
   2. In vivo testing
      1. Importance of in vivo models
      2. Selection of appropriate animal models
         1. Rodent models (mice and rats)
         2. Non-rodent models (dogs, primates, etc.)
         3. Transgenic and knockout models
      3. Pharmacodynamic studies in vivo
         1. Evaluating physiological responses
         2. Biomarker assessment
      4. Pharmacokinetic studies in vivo
         1. Absorption, distribution, metabolism, and excretion in organism
         2. Importance of bioavailability studies
      5. Ethical considerations in animal testing
         1. Compliance with regulatory standards
         2. Alternative approaches to reduce animal use
   3. Toxicology studies
      1. Acute toxicity studies
         1. Determination of LD50
         2. Single dose study designs
      2. Chronic toxicity studies
         1. Repeated dose testing
         2. Observational endpoints in long-term studies
      3. Carcinogenicity testing
         1. Species selection for oncogenic potential
         2. Tumorigenicity assessments
      4. Genotoxicity testing
         1. Assessment of DNA damage
         2. Chromosomal aberration tests
      5. Reproductive and developmental toxicity
         1. Embryo-fetal development studies
         2. Impact on fertility and reproductive capability
      6. Safety pharmacology
         1. Cardiovascular assessments
         2. Respiratory and neurological system evaluations
   4. ADME (Absorption, Distribution, Metabolism, and Excretion) profiling
      1. Importance of ADME in drug development
      2. Absorption studies
         1. Gastrointestinal tract absorption
         2. Use of Caco-2 cell models
      3. Distribution studies
         1. Rate and extent of tissue distribution
         2. Blood-brain barrier penetration
      4. Metabolism studies
         1. Role of liver enzymes such as cytochrome P450
         2. Identification of metabolites
      5. Excretion studies
         1. Renal and biliary excretion pathways
         2. Factors affecting excretion rate
      6. Integration of ADME data into PK/PD modeling
         1. Impact of ADME analysis on dosing regimen planning
         2. Use of physiologically-based pharmacokinetic (PBPK) models