A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay.

A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay. Comb Chem High Throughput Screen. 2013 Feb 27; Authors: Chau DM, Shum D, Radu C, Bhinder B, Gin D, Gilchrist ML, Djaballah H, Li YM Abstract The Notch pathway plays a crucial role in cell fate decisions through controlling various cellular processes. Overactive Notch signal contributes to cancer development from leukemias to solid tumor. γ-Secretase is an intramembrane protease responsible for the final proteolytic step of Notch that releases the membrane-tethered Notch fragment for signaling. Therefore, γ-Secretase is an attractive drug target in treating Notch-mediated cancers. However, the absence of high-throughput γ-Secretase assay using Notch substrate has limited the identification and development of γ-Secretase inhibitors that specifically target the Notch signaling pathway. Here, we report on the development of a 1536-well γ-Secretase assay using a biotinylated recombinant Notch1 substrate. We effectively assimilated and miniaturized this newly developed Notch1 substrate with the AlphaLISA detection technology and demonstrated its robustness with a calculated Z score of 0.66. We further validated this optimized assay by performing a pilot screening against a chemical library consisting of ~5,600 chemicals and identified known γ-secretase inhibitors e.g. DAPT, and Calpeptin; as well as a novel γ-secretase inhibitor referred to as KD-I-...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research

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Publication date: Available online 9 October 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Andrew Tiu, Vinicius Jorge, Peter Moussa, Djeneba Audrey Djibo, Sorab Gupta, Onder Alpdogan, Claudia Dourado
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
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Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
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Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research
Memorial Sloan Kettering Cancer Center in New York City has begun recruiting patients with pleural mesothelioma for its latest — and potentially most promising — clinical trial involving T-cell therapy. The novel study stems from the U.S. Food and Drug Administration’s recent Investigational Drug Application approval of ATA2271, a chimeric antigen receptor known as CAR T-cell therapy. This latest therapy will be tested in a phase I, dose-escalation clinical trial. It will involve the removal and genetic modification of a patient’s T cells, a type of white blood cell, that will be separated in the la...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
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Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
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