Objectives

1 Overview and Techniques: Provide a

historical and methodological review of
CADD, including structure-based and
ligand-based approaches, molecular
modeling, docking, virtual screening, QSAR,
and pharmacophore modeling.
[Link] and Machine Learning: Explore AI/ML
applications in drug interactions,
repurposing, and generative drug design.
3. Challenges: Address limitations like model
accuracy, data quality, computational costs,
and AI interpretability.
4. Integration and Validation: Highlight
multi-omics integration and the need for
experimental validation to ensure
therapeutic relevance.
5. Case Studies and Emerging Tech:
Showcase CADD success stories (e.g.,
FDA-approved drugs) and discuss
innovations like quantum computing,
AR/VR, and green chemistry.
6. Collaboration and Ethics: Advocate for
global collaborations, open-source
platforms, and address ethical/regulatory
concerns.
7. Personalized Medicine and Education:
Explore CADD's role in personalized
medicine and stress the importance of
CADD training in education.
Key Objectives of FBDD:
1. Principles and Methodologies: Focus on
fragment-based approaches, library design,
and biophysical screening techniques
(NMR, X-ray crystallography).
2. Success Stories: Highlight FDA-approved
fragment-derived oncology drugs (e.g.,
venetoclax, vemurafenib) and their impact
on "undruggable" targets.
3. Innovations and Comparisons: Discuss
fragment linking/growing strategies, AI
integration, and compare FBDD with
traditional methods like HTS.
4. Challenges and Future: Address
limitations (e.g., structural data reliance)
and explore emerging technologies
(cryo-EM, dynamic combinatorial
chemistry).
5. Resource for Researches: Provide
guidelines for fragment library design and
optimization, offering insights into the drug
development pipeline.
1. Overview of AI in Drug Discovery : To
provide a comprehensive review of how
artificial intelligence (AI), machine learning
(ML), and deep learning (DL) are
transforming drug discovery by reducing
time and costs.
2. Data and Resources: To highlight the
importance of data resources in the
pharmaceutical sector for AI-driven drug
discovery, including databases like ChEMBL,
ChemDB, and PubChem.
3. Algorithms and Techniques: To illustrate
significant AI and ML algorithms (e.g.,
supervised, unsupervised, semi-supervised,
and reinforcement learning) and their
applications in drug discovery.
4. Deep Learning Models: To compare
artificial neural networks (ANNs) with deep
neural networks (DNNs) and discuss their
roles in drug discovery.
5. Applications in Drug Discovery: To
explore the use of AI and DL in various
stages of drug discovery, such as:
- Identification of drug targets and
prediction of their structures.
- Design of drug molecules (e.g., de novo
drug design).
- Estimation of drug-target interactions
(DTIs) and binding affinity.
- Prediction of drug toxicity and ADMET
(absorption, distribution, metabolism,
excretion, toxicity) properties.
- Estimation of drug-drug interactions
(DDIs).
6. Success Stories: To showcase examples
of AI-designed molecules that have entered
clinical trials, demonstrating the practical
impact of AI in drug development.
7. Collaborations: To discuss collaborations
between pharmaceutical companies and
technology firms, emphasizing how these
partnerships accelerate drug discovery.
8. Challenges: To address the challenges in
AI-driven drug discovery, including data
quality, model interpretability,
computational constraints, and the need for
skilled workforce.
1. Define and Promote Green Chemistry: To
explain the principles of green chemistry
and their role in reducing hazardous
substances throughout a chemical
product’s lifecycle.
2. Waste Prevention: To highlight strategies
for minimizing waste generation in chemical
synthesis, including continuous flow
processing, one-pot syntheses, and solvent
recycling.
3. Atom Economy and Efficiency: To
discuss metrics like atom economy (AE),
Reaction Mass Efficiency (RME), and Green
Aspiration Level (GAL) for evaluating
synthetic efficiency.
4. Safer Chemical Syntheses: To advocate
for less hazardous reagents, solvents, and
processes, emphasizing "benign by design"
approaches and computational toxicity
modeling.
5. Sustainable Solvents and Auxiliaries: To
review greener alternatives (e.g., bio-based
solvents, supercritical fluids, ionic liquids)
and methods to reduce solvent dependence
(e.g., mechanochemistry, sonochemistry).
6. Energy Efficiency: To explore techniques
like photochemistry, microwave irradiation,
and flow chemistry that lower energy
consumption.
7. Renewable Feedstocks: To emphasize the
shift from petrochemicals to bio-based and
biodegradable materials in chemical
synthesis.
8. Reducing Derivatives: To promote
strategies like chemoselective reactions,
flow chemistry, and click chemistry to
minimize protection/deprotection steps.
9. Catalysis: To showcase catalytic methods
(metal, zeolite, biocatalysis) as sustainable
alternatives to stoichiometric reagents.
10. Biodegradability: To integrate
biodegradability into chemical design, using
predictive tools and structural
modifications for safer environmental
breakdown.
11. Green Analytical Chemistry (GAC): To
advance real-time, low-waste analytical
techniques (e.g., SFE, UHPLC,
spectroscopy) for sustainable lab practices.
12. Accident Prevention: To mitigate risks in
chemical processes through hazard
assessment, safer reagents, and
closed-system technologies like flow
chemistry.
1. Overview of Lipid-based Nanoparticle
Platforms
- Highlight the biological properties of
lipid-based nanoparticles (e.g.,
biocompatibility, biodegradability, low
immunogenicity).
- Discuss the structure and function of
liposomes, including their ability to deliver
both hydrophilic and hydrophobic drugs.
- Explain the significance of PEGylated
lipids in enhancing circulation time and
tumor accumulation, using Doxil®/Caelyx as
an example.
- Explore surface modifications (e.g.,
ligands, antibodies) for targeted drug
delivery and stimuli-responsive designs
(e.g., light, temperature, pH, enzymes).
- Identify challenges in clinical
applications (e.g., rapid clearance,
instability, high production cost).
2. Examination of Polymer-based
Nanoparticle Platforms
- Describe the advantages of
polymer-based nanoparticles (e.g., small
size, biocompatibility, prolonged
circulation, high drug-loading capacity).
- Classify polymer-based nanomedicine
into three groups: polymer-drug
conjugates, polymeric micelles, and
polyplexes/polymersomes.
- Discuss the Enhanced Permeability and
Retention (EPR) effect for passive tumor
targeting.
- Provide examples of clinical applications,
such as poly(L-glutamic acid)-paclitaxel
(Xyotax®).
- Address challenges in polymer design
(e.g., controlled degradation, polymerization
methods, site-specific conjugation).
3. Analysis of Protein-based Nanoparticle
Platforms
- Emphasize the benefits of protein-based
nanoparticles (e.g., biocompatibility,
biodegradability, low toxicity).
- List common proteins used in drug
delivery systems (e.g., viral capsids,
albumin, ferritin).
- Highlight the advantages of protein
cages (e.g., uniform size, multifunctional
surface groups, superior pharmacokinetics).
- Focus on albumin as a versatile carrier,
noting its stability, tumor uptake, and
clinical examples like Abraxane.
4. Comparative Discussion of Nanoparticle
Platforms
- Compare the strengths and limitations of
lipid-based, polymer-based, and
protein-based nanoparticles.
- Provide insights into their respective
clinical applications and ongoing research.
5. Reference to Key Studies and Clinical
Trials
- Cite relevant research and clinical trials
to support the discussion on each
nanoparticle platform.
6. Identification of Future Directions
- Outline unresolved challenges and
potential advancements in
nanoparticle-based drug delivery systems
(DDS).

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Chiranjib Chakraborty, Manojit

Bhattacharya, Sang-Soo Lee, Zhi-Hong
Wen, Yi-Hao Lo Year: 2024 Container:
Molecular Therapy — Nucleic Acids
Publisher: Cell Press Page: 102295-102295

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