A Science and Risk Based Proposal for Understanding Scale and Equipment Dependencies of Small Molecule Drug Substance Manufacturing Processes

Targeted Protein Degradation (TPD) is an emerging new modality of drug discovery that offers unprecedented therapeutic benefits over traditional protein inhibition. Most importantly, TPD unlocks the untapped pool of the proteome that to date has been considered undruggable. Captor Therapeutics (Captor) is the fourth global, and first European, company that develops small molecule drug candidates based on the principles of targeted protein degradation. Captor is located in Basel, Switzerland and Wroclaw, Poland and exploits the best opportunities of the two sites – experience and non-dilutive European grants, and talent pool, respectively. Through over $38 M of funding, Captor has been active in three areas of TPD: molecular glues, bi-specific degraders and direct degraders, ObteronsTM.

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Holistic Drug Design for Multiparameter Optimization in Modern Small Molecule Drug Discovery

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2021.128003 ◽

2021 ◽

pp. 128003

Author(s):

Lewis D. Pennington ◽

Ingo Muegge

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Small Molecule ◽

Small Molecule Drug ◽

Multiparameter Optimization

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Enabling rapid COVID-19 small molecule drug design through scalable deep learning of generative models

The International Journal of High Performance Computing Applications ◽

10.1177/10943420211010930 ◽

2021 ◽

pp. 109434202110109

Author(s):

Sam Ade Jacobs ◽

Tim Moon ◽

Kevin McLoughlin ◽

Derek Jones ◽

David Hysom ◽

...

Keyword(s):

Small Molecule ◽

Molecular Design ◽

Turnaround Time ◽

Generative Models ◽

Quality Model ◽

Training Time ◽

Small Molecule Drug ◽

Training Approach ◽

Previous State ◽

Multi Level

We improved the quality and reduced the time to produce machine learned models for use in small molecule antiviral design. Our globally asynchronous multi-level parallel training approach strong scales to all of Sierra with up to 97.7% efficiency. We trained a novel, character-based Wasserstein autoencoder that produces a higher quality model trained on 1.613 billion compounds in 23 minutes while the previous state of the art takes a day on 1 million compounds. Reducing training time from a day to minutes shifts the model creation bottleneck from computer job turnaround time to human innovation time. Our implementation achieves 318 PFLOPs for 17.1% of half-precision peak. We will incorporate this model into our molecular design loop enabling the generation of more diverse compounds; searching for novel, candidate antiviral drugs improves and reduces the time to synthesize compounds to be tested in the lab.

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Glossary and tutorial of xenobiotic metabolism terms used during small molecule drug discovery and development (IUPAC Technical Report)

Pure and Applied Chemistry ◽

10.1515/pac-2018-0208 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Paul Erhardt ◽

Kenneth Bachmann ◽

Donald Birkett ◽

Michael Boberg ◽

Nicholas Bodor ◽

...

Keyword(s):

Drug Discovery ◽

Small Molecule ◽

Chemical Structure ◽

Early Stage ◽

Xenobiotic Metabolism ◽

Drug Discovery And Development ◽

Small Molecule Drug ◽

Technical Report ◽

Wide Range ◽

Draft Version

Abstract This project originated more than 15 years ago with the intent to produce a glossary of drug metabolism terms having definitions especially applicable for use by practicing medicinal chemists. A first-draft version underwent extensive beta-testing that, fortuitously, engaged international audiences in a wide range of disciplines involved in drug discovery and development. It became clear that the inclusion of information to enhance discussions among this mix of participants would be even more valuable. The present version retains a chemical structure theme while expanding tutorial comments that aim to bridge the various perspectives that may arise during interdisciplinary communications about a given term. This glossary is intended to be educational for early stage researchers, as well as useful for investigators at various levels who participate on today’s highly multidisciplinary, collaborative small molecule drug discovery teams.

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