Abstract
Background: The Early drug discovery process was majorly phenotypic, lacking target specificity, and mechanism of action causing short and/or long-term toxicological impacts on the patients leading to several drug withdrawals from the market. Biochemical procedures and methods used in drug discovery and development make it lengthy in terms of time requiring approx. 15 years with the investment of billions of dollars for a new drug molecule. Technological advancement leading to the identification of protein structures through crystallography paved a new path toward targeted drug discovery. Objective: This paper provides a brief overview of the use of the fluorescence thermal shift assay (FTSA) as a high throughput (HTS) screening technique in small molecule drug discovery. Methods: The article discusses the principles of thermal denaturation techniques and how they are applied in drug discovery. It highlights the advantages of FTSA over other biophysical methods, including its label-free, cost-effective, and high HTS nature. The review also presents a comparative analysis of FTSA with techniques such as isothermal titration calorimetry (ITC), mass spectrometry (MS), nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), X-ray crystallography(X-RD), circular dichroism (CD), and differential scanning calorimetry (DSC). Results: The FTSA technique is described as a powerful tool that addresses the limitations of larger protein requirements, specific assay development, and low HTS associated with other thermal denaturation methods. Unlike biochemical and cellular assays that measure secondary effects, FTSA directly estimates the binding of small molecules to target proteins. Conclusion: The review concludes that FTSA is the only biophysical method that satisfies the three key prerequisites of being label-free, cost-effective, and suitable for high HTS screening in small molecule drug discovery.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.