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Author Archive | xchem-editor

April 13, 2021

Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening

April 12th 2021|J.Med.Chem 2021|Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening Bispecific degraders (PROTACs) of ERα are expected to be advantageous over current inhibitors of ERα signaling (aromatase inhibitors/SERMs/SERDs) used to treat ER+ breast cancer. Information from DNA-encoded chemical library (DECL) screening provides a method to identify novel PROTAC […]

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March 10, 2021

Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy

  March 8th 2021| J. Med. Chem. 2021| Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy Mer is a member of the TAM (Tyro3, Axl, Mer) kinase family that has been associated with cancer progression, metastasis, and drug resistance. Their essential function in immune homeostasis has prompted an interest in their […]

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March 10, 2021

Discovery of 2,4-1H-Imidazole Carboxamides as Potent and Selective TAK1 Inhibitors

  March 3rd 2021|ACS Med.Chem. Lett.2021| Discovery of 2,3-1H-Imidazole Carboxamides as Potent and Selective TAK1 Inhibitors Herein we report the discovery of 2,4-1H-imidazole carboxamides as novel, biochemically potent, and kinome selective inhibitors of transforming growth factor β-activated kinase 1 (TAK1). The target was subjected to a DNA-encoded chemical library (DECL) screen. After hit analysis a […]

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February 11, 2021

Full-length in meso structure and mechanism of rat kynurenine 3-monooxygenase inhibition

February 4th 2021 | Nature | Full-length in meso structure and mechanism of rat kynurenine 3-monooxygenase inhibition The structural mechanisms of single-pass transmembrane enzymes remain elusive. Kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases. Here, we report the mammalian full-length structure of KMO […]

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February 11, 2021

Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition

  December 17th, 2020 | Nature | Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition Protease-activated receptor-2 (PAR2) has been implicated in multiple pathophysiologies but drug discovery is challenging due to low small molecule tractability and a complex activation mechanism. Here we report the pharmacological profiling of a potent new agonist, suggested […]

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October 1, 2020

Proteros Biostructures and X-Chem to offer Comprehensive Joint Target-to-Lead Drug Discovery Services

Munich, Germany and Waltham, Mass –October 1, 2020 – Proteros Biostructures GmbH (Proteros) and X-Chem, Inc. (X-Chem) announced today the launch of an alliance with the goal of offering Hit-Identification and Target-to-Lead drug discovery services based on their complementary technology platforms. The alliance combines Proteros’ strengths in protein sciences, structural biology (crystallography and CryoEM), and […]

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July 22, 2020

X-Chem Announces Achievement of Milestone In Orexia Collaboration

Waltham, Mass – July 22, 2020 – X-Chem, Inc. (X-Chem), the global leader in DNA-encoded small molecule library screening and drug discovery, announced today that it has met a key development milestone in its collaboration with Orexia Limited (Orexia), a company focused on developing orexin positive modulators using unique structure based drug design capabilities.

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July 21, 2020

J Med Chem Novel Autotaxin Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis: A Clinical Candidate Discovered Using DNA-Encoded Chemistry

The activity of the secreted phosphodiesterase autotaxin produces the inflammatory signaling molecule LPA and has been associated with a number of human diseases including idiopathic pulmonary fibrosis (IPF). We screened a single DNA-encoded chemical library (DECL) of 225 million compounds and identified a series of potent inhibitors. Optimization of this series led to the discovery […]

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July 21, 2020

J Med Chem Machine Learning on DNA-Encoded Libraries: A New Paradigm for Hit Finding

June 11th 2020|J Med Chem Machine Learning on DNA-Encoded Libraries|A New Paradigm for Hit Finding DNA-encoded small molecule libraries (DELs) have enabled discovery of novel inhibitors for many distinct protein targets of therapeutic value. We demonstrate a new approach applying machine learning to DEL selection data by identifying active molecules from large libraries of commercial […]

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