Challenges and drawbacks of drug discovery and development
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Drug discovery and development faces several key challenges: - It is a lengthy, complex, and costly process with high uncertainty if a drug will succeed. - Identifying drug targets is difficult due to unknown disease pathophysiology. - Animal models often cannot fully replicate human diseases. - Patient heterogeneity makes drug testing challenging without extensive clinical data. - There is a lack of validated biomarkers to measure disease states. - Navigating regulatory guidelines from different organizations adds complexity.
Challenges and drawbacks of drug discovery and development
- 1. Challenges and Drawbacks of Drug Discovery and Development Submitted to: Dr. Devinder Kaur Submitted by: Gaurav 19mslsbf03 19mslsbf03 CUPB
- 2. Drawbacks on Drug Discovery and Development- Key points • Drug development is a lengthy, complex, and costly process, entrenched with a high degree of uncertainty that a drug will actually succeed. • The unknown pathophysiology for many nervous system disorders makes target identification challenging. • Animal models often cannot recapitulate an entire disorder or disease. • Challenges related to heterogeneity of the patient population might be alleviated with increased clinical phenotyping and endotyping. • Greater emphasis on human data might lead to improved target identification and validation. • There is a lack of validated diagnostic and therapeutic biomarkers to objectively detect and measure biological states. • Unfamiliarity with current regulatory processes for investigational new drug (IND) applications can be resolved through pre-IND meetings. • • Thirty ICH guidelines relevant to global drug development • Seventy FDA guidelines relevant to clinical research • Six guidelines that support the EU clinical trial directive. 19mslsbf03 CUPB
- 3. Challenges on Drug Discovery and Development- Key points • Unknown Biological Mechanisms and Biomarkers of Diseases. ... • Translational Failures Using Animal Models. ... • Lack of Clinical Phenotyping and Patient Stratification. ... • Inability to Rely on Published Data. ... • Inadequate Collaboration Among Academia, Industry, and Government. ... • Pipeline Challenges 19mslsbf03 CUPB
- 4. Challenges for Docking Methods • The fact that protein–ligand interactions occur in aqueous solution is generally appreciated, but not yet adequately accounted for. Especially, the simultaneous placement of explicit water molecules upon docking, accurate estimates of the water versus ligand interaction-energy balance, and the fast prediction of protonation states in binding pockets await a fully satisfactory solution. 19mslsbf03 CUPB
- 5. Challenges for Docking Methods • The consideration of a sufficient degree of protein flexibility needs to become part of standard docking approaches. This requires faster algorithms. In addition, with respect to scoring, an often overlooked aspect is that as soon as receptor flexibility is allowed, protein conformational energy changes need to be accounted for appropriately. 19mslsbf03 CUPB
- 6. Challenges for Docking Methods • Although flexible-ligand docking has already become standard, the error rate in predictions of interaction geometries is still significant for more flexible ligands. Again, more efficient algorithms would be required to sample the conformation space more thoroughly. 19mslsbf03 CUPB
- 7. References • https://www.ncbi.nlm.nih.gov/books/NBK195 047/ • Cavasotto, Claudio N. - In silico drug discovery and design _ theory, methods, challenges, and applications-CRC Press (2016) 19mslsbf03 CUPB