208 - How Drugs Are Designed, Targets, Phenotypes, and Structure Based Design

In this episode, Jesse Gordon-Blake, PhD, delves into the intricacies of medicinal chemistry, particularly focusing on drug discovery for ALS (amyotrophic lateral sclerosis). Jesse explains the process of discovering molecules that modulate biological pathways, the difference between structure-based and phenotype-based drug design, and the role computational methods play in drug development. The conversation also explores the challenges of crossing the blood-brain barrier, the importance of validating target response, and the complexities of progressing from a theoretical compound to preclinical studies. Additionally, Jesse touches on the significance of target product profiles, CNS drug design characteristics, and the iterative nature of medicinal chemistry. He concludes by discussing his current projects at Cortex, including fundraising strategies and timelines for drug development.

00:00 Introduction to Medicinal Chemistry

00:37 Drug Discovery Approaches

02:01 Computational Methods in Medicinal Chemistry

03:21 Challenges in ALS Drug Discovery

04:23 Blood-Brain Barrier and Drug Design

05:29 Key Properties for CNS Drug Design

08:58 Day-to-Day in Drug Discovery

09:45 Early Stage Drug Development

12:28 Validating Drug Targets

16:15 From Theory to Animal Testing

22:46 Funding and Timeline Considerations

25:45 Regulatory and Manufacturing Considerations

28:32 Conclusion and Contact Information

Dr. Jesse Gordon-Blake is an independent biotechnology and drug discovery consultant with expertise in medicinal chemistry and neurotherapeutics. He has led efforts in small molecule and peptide therapeutic development, AI-enabled drug discovery, and biotech startup formation, and currently serves as the CSO of Cortexa Therapeutics. He earned his PhD in Medicinal Chemistry from the University of Illinois at Chicago, focusing on developing innovative small-molecule enzyme modulators for Alzheimer’s disease.

https://www.linkedin.com/in/jesse-gordon-blake-phd-52a26274/

https://www.cortexatherapeutics.com/

Subhi Saadeh is a Quality Professional and host of Let's Combinate. With a background in Quality, Manufacturing Operations and R&D he's worked in Large Medical Device/Pharma organizations to support the development and launch of Hardware Devices, Disposable Devices, and Combination Products for Vaccines, Generics, and Biologics. Subhi serves currently as the International Committee Chair for the Combination Products Coalition(CPC) and as a member of ASTM Committee E55 and also served as a committee member on AAMI's Combination Products Committee.For questions, inquiries or suggestions please reach out at letscombinate.com or on the show's LinkedIn Page.