Isomorphic Labs Prepares AI-Designed Drugs for Initial Human Trials
š° Original title: AI-Designed Drugs by a DeepMind Spinoff Are Headed to Human Trials
š¤ IA: It's not clickbait ā
š„ Usuarios: It's not clickbait ā
View full AI summary: https://killbait.com/en/isomorphic-labs-prepares-ai-designed-drugs-for-initial-human-trials/?redirpost=c1ae24f9-16bf-4d11-9945-74a5c43d86bb
Isomorphic Labs Prepares AI-Designed Drugs for Initial Human Trials
š° Original title: AI-Designed Drugs by a DeepMind Spinoff Are Headed to Human Trials
š¤ IA: It's not clickbait ā
š„ Usuarios: It's not clickbait ā
View full AI summary: https://killbait.com/en/isomorphic-labs-prepares-ai-designed-drugs-for-initial-human-trials/?redirpost=c1ae24f9-16bf-4d11-9945-74a5c43d86bb
Part 27, drug discovery on an āUndruggableā Target. KāRas is a small intracellular GTPase that functions as a molecular switch, activating mitogenic signaling pathways in response to growth factors. Direct attempts to inhibit this oncogene with competitive drugs at its GTPābinding site failed because of its picomolar affinity for GTP and the high intracellular GTP concentration. Mutations in the KāRas pathway, such as KāRasG12C, render the protein constitutively active, driving uncontrolled proliferation and e.g. contributing to ~40% of KāRasādriven lung cancers. Until 2013, KāRas was considered nonādruggable, but this view shifted when the Shokat lab revealed a hidden allosteric regulatory pocket in KāRasG12C that becomes accessible when small electrophilic molecules covalently bind the mutant cysteine. This covalent engagement displaces key āprotein switches,ā biases the protein toward GDP over GTP conformation and prevents Raf binding, thereby shutting down MAPK signaling. Following this breakthrough, Amgen optimized the Shokat groupās early acrylamide fragments into an ināvivoāsuitable tool compound, ARSā1620. Extensive crystallography and docking guided the medicinal chemistry cycles that ultimately produced the highly decorated drug sotorasib (approved in 2021). In phase 3 trials in KāRasG12Cāmutant lung cancer, sotorasib improved progressionāfree survival compared with docetaxel, although overall survival was unchanged. That outcome is somewhat disappointing, but there is hope that realāworld drug combination strategies may yet deliver meaningful gains in overall survival.
Another interesting #SciComm post by Stan Van Boeckel! K-Ras #DrugDiscovery from being considered #Undruggable to the clinical approval of the #covalent #inhibitor Sotorasib.
#Science #ScienceCommunication #Medicines #StoryTelling #Cancer #KRAS #CovalentInhibitor
Part 27, drug discovery on an āUndruggableā Target. KāRas is a small intracellular GTPase that functions as a molecular switch, activating mitogenic signaling pathways in response to growth factors. Direct attempts to inhibit this oncogene with competitive drugs at its GTPābinding site failed because of its picomolar affinity for GTP and the high intracellular GTP concentration. Mutations in the KāRas pathway, such as KāRasG12C, render the protein constitutively active, driving uncontrolled proliferation and e.g. contributing to ~40% of KāRasādriven lung cancers. Until 2013, KāRas was considered nonādruggable, but this view shifted when the Shokat lab revealed a hidden allosteric regulatory pocket in KāRasG12C that becomes accessible when small electrophilic molecules covalently bind the mutant cysteine. This covalent engagement displaces key āprotein switches,ā biases the protein toward GDP over GTP conformation and prevents Raf binding, thereby shutting down MAPK signaling. Following this breakthrough, Amgen optimized the Shokat groupās early acrylamide fragments into an ināvivoāsuitable tool compound, ARSā1620. Extensive crystallography and docking guided the medicinal chemistry cycles that ultimately produced the highly decorated drug sotorasib (approved in 2021). In phase 3 trials in KāRasG12Cāmutant lung cancer, sotorasib improved progressionāfree survival compared with docetaxel, although overall survival was unchanged. That outcome is somewhat disappointing, but there is hope that realāworld drug combination strategies may yet deliver meaningful gains in overall survival.
Very much looking forward to today's @LED3hub Lecture by Peng Chen on "Live-cell Protein Chemistry in Health and Disease".
If you are interested, make sure to come by!
https://www.universiteitleiden.nl/en/science/led3/led3-lectures
New Algorithmic Scrutiny Targets Molecular Migrations in Drug Development
University of Oregon's new AI tool helps drug makers test new molecules faster and cheaper. It predicts how drugs will work before lab tests.
#DrugDiscovery, #AIinPharma, #UniversityOfOregon, #MolecularModeling, #HealthcareTech
https://newsletter.tf/oregon-university-ai-speeds-up-drug-making/
This new AI tool from the University of Oregon can help create new medicines much faster than before. It uses computers to predict how molecules will behave.
#DrugDiscovery, #AIinPharma, #UniversityOfOregon, #MolecularModeling, #HealthcareTech
https://newsletter.tf/oregon-university-ai-speeds-up-drug-making/
š§© Could RNA and proteins share the same āshape languageā for binding drugs?
š Eigenvalue Ratios Reveal Shared Binding Pocket Shapes in RNA and Protein Structures. Computational and Structural Biotechnology Journal (CSBJ). DOI: https://doi.org/10.34133/csbj.0022
š CSBJ - A Science Partner Journal: https://spj.science.org/journal/csbj
#DrugDiscovery #StructuralBiology #ComputationalBiology #RNAResearch #ProteinScience #Bioinformatics #MolecularModeling #Genomics #Proteomics #Cheminformatics #LigandBinding
OpenAI (@OpenAI)
OpenAIź° ģė¬¼ķ, ģ ģ½ ź°ė°, ģ ķģķģ ģķ ģė”ģ“ Life Sciences ėŖØėø ģė¦¬ģ¦ė„¼ ė ź¹ź² ģź°ķė¤. ģ°źµ¬ ģ± ģģ @joyjiao12ģ ģ ķ ģ± ģģ Yunyun Wangģ“ OpenAI Podcastģ ģ¶ģ°ķ“ ė°ģ“ģ¤ ė¶ģ¼ģ© ėŖØėø źµ¬ģ¶ ė°©ķ„ź³¼ ķģ© ź°ė„ģ±, ģ°źµ¬ ė° ģ ķ ź“ģ ģ ė ¼ģķė¤.
To go deeper on our new Life Sciences model series, research lead @joyjiao12 and product lead Yunyun Wang joined @AndrewMayne on the OpenAI Podcast to discuss how weāre building models for biology, drug discovery, and translational medicine. They cover both the opportunity and
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