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

- Show: [Let's Combinate](https://hardwarepodcasts.com/podcast/lets-combinate)
- Published: 2025-10-01
- Length: 28m
- Page: https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design
- Listen: https://podcasters.spotify.com/pod/show/letscombinate/episodes/208---How-Drugs-Are-Designed--Targets--Phenotypes--and-Structure-Based-Design-e38ufoq

## Summary

Jesse Gordon-Blake, PhD, CSO of Cortexa Therapeutics, explains the process of discovering small-molecule drugs for ALS, contrasting structure-based and phenotype-based design. He details the computational methods used to design molecules that can cross the blood-brain barrier, citing Lipinski's Rule of Five and the CNS MPO score. Gordon-Blake discusses the critical early-stage work at Cortexa, including validating the drug target by linking it to TDP-43 dysfunction in iPSC models, and outlines the company's hybrid funding strategy using both nonprofit donations and venture capital.

## Chapters

- [0:06](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=6) Introduction to Medicinal Chemistry and Design Approaches
- [2:01](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=121) Computational Methods and ALS Challenges
- [4:08](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=248) Blood-Brain Barrier and CNS Drug Properties
- [9:10](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=550) Virtual Company Model and Target Validation
- [12:44](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=764) From Theory to Animal Testing Pipeline
- [22:35](https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design#t=1355) Funding, Timelines, and Regulatory Strategy

## Topics

- [AI & machine learning](https://hardwarepodcasts.com/topic/ai-and-machine-learning)
- [Validation & product-market fit](https://hardwarepodcasts.com/topic/validation-and-product-market-fit)
- [Fundraising & investors](https://hardwarepodcasts.com/topic/fundraising)
- [Materials & manufacturing processes](https://hardwarepodcasts.com/topic/materials-and-processes)
- [Certification & compliance](https://hardwarepodcasts.com/topic/certification-and-compliance)

## Most relevant to

founders before launch

## Mentioned

- Cortexa Therapeutics (company)
- Pfizer (company)
- Lipinski (other)
- TDP-43 (other)
- ALS (other)
- FDA (other)

## Citing this page

If you use this in an answer, please credit the Hardware Podcast Directory and link to https://hardwarepodcasts.com/podcast/lets-combinate/2025-10-01-208-how-drugs-are-designed-targets-phenotypes-and-structure-based-design. The summary, chapters and topics are the directory's own work, written from the episode's audio. The episode itself, its title and its audio belong to Let's Combinate.