scholarly journals Electrically Triggered Release of a Small Molecule Drug from a Polyelectrolyte Multilayer Coating

2010 ◽  
Vol 22 (23) ◽  
pp. 6416-6425 ◽  
Author(s):  
Daniel J. Schmidt ◽  
Joshua S. Moskowitz ◽  
Paula T. Hammond
Keyword(s):  
Small Molecule ◽  
Multilayer Coating ◽  
Triggered Release ◽  
Polyelectrolyte Multilayer ◽  
Small Molecule Drug

Characterization and Preclinical Perspectives of Organic Small Molecule Drug Metabolites in Drug-drug Interactions

2016 ◽  
Vol 20 (17) ◽  
pp. 1827-1834
Author(s):  
Liqian Gao ◽  
Jun Chen ◽  
Yi Hu ◽  
Hongyan Sun ◽  
Yong Siang Ong ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Small Molecule ◽  
Drug Metabolites ◽  
Small Molecule Drug

Targeted Protein Degradation: "The Gold Rush is On!"

2020 ◽  
Vol 7 (1) ◽  
pp. 4-16
Author(s):  
Daria Kotlarek ◽  
Agata Pawlik ◽  
Maria Sagan ◽  
Marta Sowała ◽  
Alina Zawiślak-Architek ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Protein Degradation ◽  
Small Molecule ◽  
Gold Rush ◽  
European Company ◽  
Drug Candidates ◽  
Protein Inhibition ◽  
Small Molecule Drug ◽  
Therapeutic Benefits ◽  
Talent Pool

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.

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

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.

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

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.

STEM-12. THE SMALL MOLECULE DRUG CBL0137 INCREASES THE LEVEL OF DNA DAMAGE AND THE EFFICACY OF RADIOTHERAPY FOR GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Miranda Tallman ◽  
Abby Zalenski ◽  
Amanda Deighen ◽  
Treg Grubb ◽  
Morgan Schrock ◽  
...  
Keyword(s):  
Dna Damage ◽  
Small Molecule ◽  
Small Population ◽  
Orthotopic Model ◽  
Average Life Expectancy ◽  
Small Molecule Drug ◽  
Specific Cytotoxicity ◽  
Treatment Paradigm ◽  
New Treatment

Abstract Glioblastoma (GBM) is a fatal and incurable brain tumor, with an average life expectancy after diagnosis of only 12-15 months. A main reason for the lethality of GBM is inevitable recurrence, caused by a small population of the tumor cells, called cancer stem cells (CSCs). These cells are aggressive, infiltrative, and resistant to current GBM treatments of chemotherapy and radiotherapy. We use a small molecule drug, CBL0137, which inhibits the FACT (facilitates chromatin transcription) complex leading to cancer cell specific cytotoxicity. Here, we show that CBL0137 sensitized GBM CSCs to radiotherapy and hence lead to increased CSC death and prolonged survival in preclinical models. Clonogenic assays were used to show that CSCs were radiosensitized after CBL0137 treatment. We saw increased DNA damage when GBM CSCs were treated with CBL0137, as well as a decrease in foci resolution over time, when CBL0137 was combined with irradiation. In order to elucidate if the increase in DNA damage was directly due to the inhibition of the FACT complex, we depleted the level of FACT in our GBM CSCs. FACT depletion also led to increased DNA damage, and even more so when combined with irradiation. To validate whether combination therapy sensitized CSCs to radiotherapy in vivo, we used a subcutaneous mouse model and showed combination treatment decreased CSCs frequency in these tumors as well as decreased tumor volume. With an orthotopic model of GBM, we showed that CBL0137 treatment followed by radiotherapy significantly increased survival of mice bearing tumors over either treatment alone. Together, this work establishes a new treatment paradigm for GBM, which sensitizes radio-resistant GBM CSCs to irradiation, a critical component of patient care. Radio-sensitizing agents, including CBL0137, pose an exciting new therapeutic capable of increasing the efficacy of irradiation, by inclusively targeting CSCs.

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