7 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.

High-throughput screening (HTS) assays described herein rely on structural alterations triggered by cTnI phosphorylation during beta-adrenergic stimulation. These HTS assays may be used to pinpointsmall molecules that emulate phosphorylation effects, amplifying lusitropy by accelerating calcium dissociation from thin filaments. With a focus on addressing diastolic dysfunction, especially in conditions like HCM, the aim is to determine compounds tailored to modulate diastolic performance.

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.

The application discloses the development of scalable thiol reactivity (STRP), a method which enables the facile interrogation of large chemical libraries for intrinsic reactivity with cysteine. The application further discloses high throughput screening assays using STRP identified azetidinyl oxadiazole as a moiety that selectively reacts with cysteine through a ring opening-based mechanism, capable of covalently engaging cysteine residues broadly across the human proteome. The application further discloses an azetidinyl oxadiazole containing small molecule that augments the catalytic activity of the deubiquitinase UCHL1 in vitro and in cells by covalently modifying a cysteine distal to its enzymatic active site.