5 results about "High-Throughput Screening Assays" patented technology

UBAS is a critical El-activating enzyme in the UFMylation pathway, a post-translational modification process implicated in neurodegenerative diseases and cancers. Here, a high-throughput screening (HTS) assay was developed to identify inhibitors of UBAS from various compound libraries. Eighteen novel UBAS inhibitors were identified, belonging to several distinct chemical scaffolds with low micromolar IC50 values. These inhibitors demonstrated selectivity for UBAS over other El enzymes, including UBA1, and showed efficacy in inhibiting endogenous UFMylation in HEK293T cells. The identified inhibitors not only provided valuable tools for studying UFMylation but also represented potential therapeutic candidates for diseases associated with dysregulated UFMylation, such as Alzheimer's disease and cancer.

The method as disclosed herein utilizes a high throughput screening assay (GigaAssay) to produce a comprehensive mutation effect on gene activity (MEGA)-mutation activity profile (Map). The methods as disclosed herein can be used to assess the mutational effect for any gene, under any condition (e.g., drug treatment) with any assay in mammalian cells in culture. Thus, the methods provided herein can be utilized to discover and screen dominant negative variants, and provide a reliable solution to the problem of identifying unique pharmacologically active variants of proteins. Furthermore, the method provided herein can be integrated to cell-based assays to investigate disease pathology and test potential drugs.

Compositions and methods are directed to a diverse library of barcoded constructs expressing biologies that are known to be challenging to express. A high throughput screening assay is also disclosed.

Compositions and methods are directed to a diverse library of barcoded constructs expressing biologies that are known to be challenging to express. A high throughput screening assay is also disclosed.

UBAS is a critical El-activating enzyme in the UFMylation pathway, a post-translational modification process implicated in neurodegenerative diseases and cancers. Here, a high-throughput screening (HTS) assay was developed to identify inhibitors of UBAS from various compound libraries. Eighteen novel UBAS inhibitors were identified, belonging to several distinct chemical scaffolds with low micromolar IC50 values. These inhibitors demonstrated selectivity for UBAS over other El enzymes, including UBA1, and showed efficacy in inhibiting endogenous UFMylation in HEK293T cells. The identified inhibitors not only provided valuable tools for studying UFMylation but also represented potential therapeutic candidates for diseases associated with dysregulated UFMylation, such as Alzheimer's disease and cancer.