Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial
Sign Up to like & getrecommendations! Published in 2018 at "JAMA Psychiatry"
DOI: 10.1001/jamapsychiatry.2017.3572
Abstract: Importance Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation… read more here.
Keywords: trial; glutamate targeted; utility; randomized clinical ... See more keywords
Beyond group differences: Exploring the preliminary signals of target engagement of an executive function training for autistic children
Sign Up to like & getrecommendations! Published in 2022 at "Autism Research"
DOI: 10.1002/aur.2735
Abstract: Understanding both for whom and how interventions work is a crucial next step in providing personalized care to children with autism spectrum disorder (ASD). Autistic children present with heterogeneity both within core ASD criteria and… read more here.
Keywords: target engagement; autistic children; executive function; function training ... See more keywords
First Fluorescent Acetylspermidine Deacetylation Assay for HDAC10 Identifies Selective Inhibitors with Cellular Target Engagement
Sign Up to like & getrecommendations! Published in 2022 at "Chembiochem"
DOI: 10.1002/cbic.202200180
Abstract: Histone deacetylases (HDACs) are important epigenetic regulators involved in many diseases, especially cancer. Five HDAC inhibitors have been approved for anticancer therapy and many are in clinical trials. Among the 11 zinc‐dependent HDACs, HDAC10 has… read more here.
Keywords: assay hdac10; deacetylation; cellular target; target engagement ... See more keywords
A High-Throughput Method to Prioritize PROTAC Intracellular Target Engagement and Cell Permeability Using NanoBRET.
Sign Up to like & getrecommendations! Published in 2021 at "Methods in molecular biology"
DOI: 10.1007/978-1-0716-1665-9_14
Abstract: Target engagement and cell permeation are important parameters that may limit the efficacy of proteolysis-targeting chimeras (PROTACs). Here, we present an approach that facilitates both the quantitation of PROTAC binding affinity for an E3 ligase… read more here.
Keywords: engagement cell; target engagement; target; using nanobret ... See more keywords
Quantitative Assessment of the Target Engagement of a KRAS G12C Inhibitor in Formalin-Fixed Paraffin-Embedded Tumor Tissues Using Immunoaffinity Capture 2D-LC-MS/MS.
Sign Up to like & getrecommendations! Published in 2025 at "Analytical chemistry"
DOI: 10.1021/acs.analchem.5c02696
Abstract: Understanding the target engagement of covalent inhibitors, such as KRAS G12C inhibitors, is essential for evaluating their mechanisms of action and efficacy, particularly given the KRAS G12C mutation's significant role in cancer progression. We previously… read more here.
Keywords: formalin fixed; kras g12c; fixed paraffin; target engagement ... See more keywords
Discovery of 2-(3-Benzamidopropanamido)thiazole-5-carboxylate Inhibitors of the Kinesin HSET (KIFC1) and the Development of Cellular Target Engagement Probes
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c01591
Abstract: The existence of multiple centrosomes in some cancer cells can lead to cell death through the formation of multipolar mitotic spindles and consequent aberrant cell division. Many cancer cells rely on HSET (KIFC1) to cluster… read more here.
Keywords: thiazole carboxylate; hset kifc1; chemistry; target engagement ... See more keywords
Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with In Vivo Target Engagement.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c01451
Abstract: Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of in vivo target engagement are needed to fully… read more here.
Keywords: vivo target; mertk inhibitors; azetidine benzoxazole; target ... See more keywords
Size-Dependent Target Engagement of Covalent Probes
Sign Up to like & getrecommendations! Published in 2025 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.5c00017
Abstract: Labeling proteins with covalent ligands is finding increasing use in proteomics applications, including identifying nucleophilic residues amenable for labeling and in the development of targeted covalent inhibitors (TCIs). Labeling efficiency is measured by the covalent… read more here.
Keywords: covalent; dependent target; size dependent; target engagement ... See more keywords
Challenging the "Undruggable"─Targeting STAT3 but Identifying Potent TrkA-Targeted Inhibitors.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.5c00214
Abstract: Signal transducer and activator of transcription 3 (STAT3) is a promising yet challenging anticancer drug target due to its complex signaling and limited "druggability". To this end, we herein highlight a target engagement-focused screening and… read more here.
Keywords: undruggable targeting; challenging undruggable; trka; stat3 ... See more keywords
Real-Time Cellular Thermal Shift Assay to Monitor Target Engagement
Sign Up to like & getrecommendations! Published in 2022 at "ACS Chemical Biology"
DOI: 10.1021/acschembio.2c00334
Abstract: Determining a molecule’s mechanism of action is paramount during chemical probe development and drug discovery. The cellular thermal shift assay (CETSA) is a valuable tool to confirm target engagement in cells for a small molecule… read more here.
Keywords: cellular thermal; real time; target engagement; cetsa ... See more keywords
Discovery of a Small Molecule TREM2 Agonist with Improved In Vitro Pharmacokinetic Profile and Validated Target Engagement.
Sign Up to like & getrecommendations! Published in 2025 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.5c00299
Abstract: The microglial lipid-sensing receptor TREM2 is a promising therapeutic target for Alzheimer's disease. We report the discovery of C1, a racemic structural analog of the clinical-stage TREM2 agonist VG-3927. Synthesized via a concise, modular, and… read more here.
Keywords: vitro pharmacokinetic; pharmacokinetic profile; target; validated target ... See more keywords