899713-86-1 Usage
Description
M348 is a reversible LYPLA1 inhibitor that selectively targets the lysophospholipase 1 enzyme over lysophospholipase 2 with a 14-fold selectivity. It exhibits minimal activity against a panel of more than 20 other serine hydrolases, making it a specific inhibitor for its intended target.
Uses
Used in Pharmaceutical Industry:
M348 is used as a research tool for studying the role of LYPLA1 in various biological processes and its potential as a therapeutic target for treating diseases associated with its dysregulation.
Used in Drug Development:
M348 is used as a lead compound in the development of new drugs targeting LYPLA1, which may have potential applications in treating metabolic disorders, inflammatory conditions, and other diseases where LYPLA1 activity is implicated.
Used in Biochemical Research:
M348 is used as a biochemical probe to investigate the enzymatic activity, substrate specificity, and regulation of LYPLA1, contributing to a better understanding of its role in cellular processes and disease mechanisms.
Biochem/physiol Actions
ML348 is a substrate-competitive, reversible and APT1-selective acyl-protein thioesterase (APT) inhibitor (IC50/Ki = 840 nM/300 nM against APT1; IC50 & Ki >10 μM against APT2). ML348 effectively inhibits cellular APT1 activity in cultures (by >95% in HEK293T & mouse T cells; 5 μM for 4 h) and in mice in vivo (by >90% in lung/heart/kidney and by ~50% in brain tissue 4 h post 50 mg/kg i.p. dosing) without affecting more than 15 cellular serine hydrolases and APT2.
Check Digit Verification of cas no
The CAS Registry Mumber 899713-86-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,9,9,7,1 and 3 respectively; the second part has 2 digits, 8 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 899713-86:
(8*8)+(7*9)+(6*9)+(5*7)+(4*1)+(3*3)+(2*8)+(1*6)=251
251 % 10 = 1
So 899713-86-1 is a valid CAS Registry Number.
899713-86-1Relevant articles and documents
Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes
Adibekian, Alexander,Martin, Brent R.,Chang, Jae Won,Hsu, Ku-Lung,Tsuboi, Katsunori,Bachovchin, Daniel A.,Speers, Anna E.,Brown, Steven J.,Spicer, Timothy,Fernandez-Vega, Virneliz,Ferguson, Jill,Hodder, Peter S.,Rosen, Hugh,Cravatt, Benjamin F.
supporting information; experimental part, p. 10345 - 10348 (2012/08/08)
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.
