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Disease Modeling and Target Discovery
1. Introduction
Introductory Lecture by Alex Zhavoronkov, PhD, founder and CEO of Insilico Medicine (31:24)
Drug Target Discovery - Definitions (8:15)
Brief History of Drug Target Discovery (8:33)
Target-centric Approach In Drug Discovery (8:55)
Drug Development Funnel (6:01)
Importance of the Target Selection: Phase 2 Failures (3:41)
Proteins and Other Types of Biological Molecules as Targets (11:51)
Who Discovers Targets in the Modern World (7:00)
Complexity and Diversity of the Target Discovery Tasks (8:32)
2. Target Selection Criteria
Mechanisms of Drug Action (10:50)
Evidences of the Target Implication in the Disease (11:24)
Therapeutic Modalities and Druggability (11:40)
Tissue Specificity (8:48)
Target Novelty vs Repurposing (11:22)
Target Feasibility (12:37)
3. Target Discovery Landscape Nowadays
Major achievements and failures of the pharma companies in the last 20 years (6:35)
Top pharma companies and their pipelines nowadays (6:00)
The most crowded and abandoned therapeutic areas. Phase transition success and likelihood of approval (8:22)
Innovation at big pharma vs small biotech (4:44)
Successful repurposing within and across disease areas (4:52)
4. Computational Approach in Target Discovery
Why Use AI for Target Selection? (7:09)
Omics Data Types - Advantages and Downsides (7:30)
Use of Biological Graphs (11:33)
Text Data and Prior Knowledge (13:08)
Examples of the Tools for Drug Target Discovery (11:53)
Applications of Single Cell Data in Drug Discovery (9:55)
Omics Data Analysis Put in the Context of Prior Knowledge (5:03)
Challenges in Multi-Omics Computational Approaches to Target Selection (6:18)
Validation of Computational Approaches to Target Selection (9:06)
5. Computational Approach in Target Discovery: Case Studies
Previous Attempts and Growing Role of Computational Methods to Meet Target Selection Criteria (14:16)
AI for Target Discovery (14:07)
AI for Target Discovery: Case Studies (25:57)
PandaOmics Target ID Page (3:52)
Exercise: Novel Small Molecules Targets for Liver Cirrhosis
Exercise: Novel Antibody Targets for Sarcoma
Exercise: Common Targets for Familial and Sporadic Amyotrophic Lateral Sclerosis
6. Target Combinations
Drug Combinations: Advantages and Downsides (10:11)
Synergistic vs additive effects (5:11)
Oncology and Synthetic Lethality (17:29)
Robotic Lab for the Rapid Discovery of Combinations (14:55)
Discovery of Drug Combination for Auto-Immune Diseases (13:34)
7. Extended Target Discovery: Current and Future Trends
New Therapeutic Modalities (20:27)
Evolution of the Druggable Genome Concept (10:49)
Untargeted to Targeted - Re-Evaluation of the Mechanism of Action and Toxicity for Old Drugs (5:02)
Indication Expansion and Prioritization (8:27)
Target Discovery and Senolytics (7:38)
Large Language Models in Drug Discovery (2:41)
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