216657-60-2

Usage

Uses

Used in Pharmaceutical Industry:
AR-C118925 is used as a research tool for studying the role of the P2Y2 receptor in various physiological and pathological processes. Its potent and selective antagonism of the P2Y2 receptor makes it a valuable compound for investigating the receptor's function and potential therapeutic applications.
Used in Drug Development:
AR-C118925 is used as a lead compound in the development of new drugs targeting the P2Y2 receptor. Its high selectivity and potency make it a promising candidate for the treatment of diseases associated with the P2Y2 receptor, such as inflammatory disorders and certain types of cancer.
Used in Research Applications:
AR-C118925 is used as a research reagent to study the molecular mechanisms underlying the P2Y2 receptor's function. It can be employed in various experimental setups, such as cell culture, animal models, and biochemical assays, to gain insights into the receptor's role in cellular signaling and disease progression.

Upstream product

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• 216658-01-4 5-{[5-(2,8-dimethyl-5H-dibenzo[a,d]cyclohepten-5-yl)-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl]methyl}-2-furancarboxylic acid ethyl ester 
• 4418-61-5 5-aminotetrazole 
• 216658-02-5 5-[[5-{2,8-Dimethyl-5H-dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-2-furancarboxylic acid ethyl ester 
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Relevant academic research and scientific papers

From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor

The G protein-coupled P2Y2 receptor, activated by ATP and UTP has been reported as a potential drug target for a wide range of important clinical conditions, such as tumor metastasis, kidney disorders, and in the treatment of inflammatory conditions. However, pharmacological studies on this receptor have been impeded by the limited reported availability of stable, potent and selective P2Y2R antagonists. This article describes the design and synthesis of AR-C118925, a potent and selective non-nucleotide antagonist of the P2Y2 receptor discovered using the endogenous P2Y2R agonist UTP as the chemical starting point.

Synthesis, characterization, and in vitro evaluation of the selective P2Y2 receptor antagonist AR-C118925

The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties. We therefore developed an improved procedure for the synthesis of AR-C118925 and two derivatives to allow up-scaling and assessed their potency in calcium mobilization assays on the human and rat P2Y2 receptors recombinantly expressed in 1321N1 astrocytoma cells. The compound was further evaluated for inhibition of P2Y2 receptor-induced β-arrestin translocation. AR-C118925 behaved as a competitive antagonist with pA2 values of 37.2?nM (calcium assay) and 51.3?nM (β-arrestin assay). Selectivity was assessed vs. related receptors including P2X, P2Y, and adenosine receptor subtypes, as well as ectonucleotidases. AR-C118925 showed at least 50-fold selectivity against the other investigated targets, except for the P2X1 and P2X3 receptors which were blocked by AR-C118925 at concentrations of about 1?μM. AR-C118925 is soluble in buffer at pH 7.4 (124?μM) and was found to be metabolically highly stable in human and mouse liver microsomes. In Caco2 cell experiments, the compound displayed moderate permeability indicating that it may show limited peroral bioavailability. AR-C118925 appears to be a useful pharmacological tool for in vitro and in vivo studies.