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
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
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
The versatility of boron in biological target engagement.
Sign Up to like & getrecommendations! Published in 2017 at "Nature chemistry"
DOI: 10.1038/nchem.2814
Abstract: Boron-containing molecules have been extensively used for the purposes of chemical sensing, biological probe development and drug discovery. Due to boron's empty p orbital, it can coordinate to heteroatoms such as oxygen and nitrogen. This… read more here.
Keywords: versatility boron; chemistry; boron biological; biological target ... See more keywords
Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis
Sign Up to like & getrecommendations! Published in 2020 at "Nature Communications"
DOI: 10.1038/s41467-020-17027-5
Abstract: Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous… read more here.
Keywords: genetics; chemical genetics; target; strategy ... See more keywords
Microneurography as a minimally invasive method to assess target engagement during neuromodulation
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Neural Engineering"
DOI: 10.1088/1741-2552/acc35c
Abstract: Objective. Peripheral neural signals recorded during neuromodulation therapies provide insights into local neural target engagement and serve as a sensitive biomarker of physiological effect. Although these applications make peripheral recordings important for furthering neuromodulation therapies,… read more here.
Keywords: microneurography; neuromodulation therapies; neuromodulation; target engagement ... See more keywords
Development of an in vivo target-engagement biomarker for TRPA1 antagonists in humans.
Sign Up to like & getrecommendations! Published in 2017 at "British journal of clinical pharmacology"
DOI: 10.1111/bcp.13143
Abstract: AIM To develop a non-invasive, safe and reproducible target-engagement biomarker for future TRPA1 antagonists in healthy volunteers. METHODS Dose finding (n = 11): 3%, 10%, and 30% cinnamaldehyde (CA) and placebo (= vehicle) was topically applied on… read more here.
Keywords: min; target engagement; engagement biomarker; trpa1 antagonists ... See more keywords
Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo‐controlled, double‐blind phase I/Ib studies in healthy subjects and patients
Sign Up to like & getrecommendations! Published in 2022 at "Clinical and Translational Science"
DOI: 10.1111/cts.13317
Abstract: RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to… read more here.
Keywords: toxicology; ripk1; subjects patients; sar443060 ... See more keywords