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Usage

Uses

Used in Pharmaceutical Industry:
ML 349 is used as a therapeutic agent for the treatment of various diseases and conditions. Its isoform selective inhibition of acyl protein thioesterases makes it a potential candidate for the development of drugs targeting specific enzyme isoforms, which can lead to more effective and targeted treatments.
Used in Research Applications:
ML 349 is also used as a research tool in the study of the role of lysophospholipase 2 and acyl protein thioesterases in various biological processes. Its selective inhibition properties allow researchers to investigate the specific functions and mechanisms of these enzymes, contributing to a better understanding of their roles in health and disease.
Used in Drug Development:
ML 349 can be utilized in the development of new drugs targeting lysophospholipase 2 and acyl protein thioesterases. Its isoform selective inhibition can potentially lead to the creation of more effective and safer drugs with fewer side effects, as it allows for the targeting of specific enzyme isoforms involved in disease processes.

Upstream product

• 38212-30-5 4-(4-methoxyphenyl)piperazine 
• 1171193-99-9 4H-thieno[3,2-c]thiochromene-2-carboxylic acid 5,5-dioxide 

Relevant academic research and scientific papers

Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes

The development of small-molecule inhibitors for perturbing enzyme function requires assays to confirm that the inhibitors interact with their enzymatic targets in vivo. Determining target engagement in vivo can be particularly challenging for poorly characterized enzymes that lack known biomarkers (e.g., endogenous substrates and products) to report on their inhibition. Here, we describe a competitive activity-based protein profiling (ABPP) method for measuring the binding of reversible inhibitors to enzymes in animal models. Key to the success of this approach is the use of activity-based probes that show tempered rates of reactivity with enzymes, such that competition for target engagement with reversible inhibitors can be measured in vivo. We apply the competitive ABPP strategy to evaluate a newly described class of piperazine amide reversible inhibitors for the serine hydrolases LYPLA1 and LYPLA2, two enzymes for which selective, in vivo active inhibitors are lacking. Competitive ABPP identified individual piperazine amides that selectively inhibit LYPLA1 or LYPLA2 in mice. In summary, competitive ABPP adapted to operate with moderately reactive probes can assess the target engagement of reversible inhibitors in animal models to facilitate the discovery of small-molecule probes for characterizing enzyme function in vivo.