1540-28-9Relevant articles and documents
Calreticulin transacetylase: A novel enzyme-mediated protein acetylation by acetoxy derivatives of 3-alkyl-4-methylcoumarins
Jalal, Sarah,Chand, Karam,Kathuria, Abha,Singh, Prabhjot,Priya, Nivedita,Gupta, Bhavna,Raj, Hanumantharao G.,Sharma, Sunil K.
, p. 131 - 136 (2012)
Our earlier investigations culminated in the discovery of a unique membrane-bound enzyme Calreticulin transacetylase (CRTAase) in mammalian cells catalyzing the transfer of acetyl group from polyphenolic acetates (PAs) to certain functional proteins viz. Glutathione S-transferase (GST), NADPH Cytochrome c reductase and Nitric oxide synthase (NOS) resulting in the modulation of their biological activities. In order to develop SAR study, herein, we studied the influence of alkyl group at C-3 position of acetoxy coumarins on the CRTAase activity. The alkylated acetoxy coumarins lead to inhibition of catalytic activity of GST, and ADP induced platelet aggregation by the way of activation of platelet Nitric oxide synthase (NOS). Furthermore, the increase in size of the coumarin C-3 alkyl group was found to decrease the CRTAase activity.
Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s)
Kulkarni, Pushkar M.,Kulkarni, Abhijit R.,Korde, Anisha,Tichkule, Ritesh B.,Laprairie, Robert B.,Denovan-Wright, Eileen M.,Zhou, Han,Janero, David R.,Zvonok, Nikolai,Makriyannis, Alexandros,Cascio, Maria G.,Pertwee, Roger G.,Thakur, Ganesh A.
, p. 44 - 60 (2016/01/29)
Undesirable side effects associated with orthosteric agonists/antagonists of cannabinoid 1 receptor (CB1R), a tractable target for treating several pathologies affecting humans, have greatly limited their translational potential. Recent discovery of CB1R negative allosteric modulators (NAMs) has renewed interest in CB1R by offering a potentially safer therapeutic avenue. To elucidate the CB1R allosteric binding motif and thereby facilitate rational drug discovery, we report the synthesis and biochemical characterization of first covalent ligands designed to bind irreversibly to the CB1R allosteric site. Either an electrophilic or a photoactivatable group was introduced at key positions of two classical CB1R NAMs: Org27569 (1) and PSNCBAM-1 (2). Among these, 20 (GAT100) emerged as the most potent NAM in functional assays, did not exhibit inverse agonism, and behaved as a robust positive allosteric modulator of binding of orthosteric agonist CP55,940. This novel covalent probe can serve as a useful tool for characterizing CB1R allosteric ligand-binding motifs.
ALLOSTERIC MODULATORS OF THE CANNIBINOID 1 RECEPTOR
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Paragraph 0269, (2015/03/13)
The present technology relates to compounds and compositions of Formulas I, II, VII, and VIII, and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of addiction, metabolic syndrome, obesity, and/or a CB1 receptor-medited disorder.