L-748,337

Names

[ Name ]:
L-748,337

[Synonym ]:
L 748,337
6-Chloromelatonin

Biological Activity

[Description]:

L748337 is a potent β3-adrenergic receptor antagonist and displays selectivity over β1 and β2 receptors. The Ki values of L748337 for β3-, β2- and β1-adrenoceptors are 4.0 nM, 204 nM and 390 nM, respectively[1]. L748337 couples predominantly to Gi to activate MAPK signaling and increases phosphorylation of Erk1/2 with pEC50 value of 11.6[2]. L748337 can be used for the research of cancer, nonalcoholic fatty liver disease (NAFLD), and cardiovascular related diseases[1][2][3].

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Metabolic Disease

[Target]

Beta-3 adrenergic receptor:4 nM (Ki)

Beta-2 adrenergic receptor:204 nM (Ki)

Beta-1 adrenergic receptor:390 nM (Ki)

[In Vitro]

L748337 (1 μM) inhibits iNOS expression in B16F10 cells[1].

[In Vivo]

L-748337 (intraperitoneal injection; 5 mg/kg; beginning 10 days until D18) decreases the growth of melanoma induced by B16F10 cell inoculation and decreases tumor vasculature in mice[1]. Animal Model: Fifty male C57BL/6 J mice (8 weeks of age) bearing syngeneic B16F10 cell[1] Dosage: 5 mg/kg Administration: Beginning 10 days until D18 Result: Exhibited anti-cancer effects.

[References]

[1]. S Neidhold, et al. The function of alpha- and beta-adrenoceptors of the saphenous artery in caveolin-1 knockout and wild-type mice. Br J Pharmacol. 2007 Feb;150(3):261-70.

[2]. Masaaki Sato, et al. The beta3-adrenoceptor agonist 4-[[(Hexylamino)carbonyl]amino]-N-[4-[2-[[(2S)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]-phenyl]-benzenesulfonamide (L755507) and antagonist (S)-N-[4-[2-[[3-[3-(acetamidomethyl)phenoxy]-2-hydroxypropyl]amino]-ethyl]phenyl]benzenesulfonamide (L748337) activate different signaling pathways in Chinese hamster ovary-K1 cells stably expressing the human beta3-adrenoceptor. Mol Pharmacol. 2008 Nov;74(5):1417-28.

[3]. Ziwen Wang, et al. The protective effects of the β3 adrenergic receptor agonist BRL37344 against liver steatosis and inflammation in a rat model of high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). Mol Med. 2020 Jun 5;26(1):54.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₆H₃₁N₃O₅S

[ Molecular Weight ]:
497.60600

[ Exact Mass ]:
497.19800

[ PSA ]:
125.14000

[ LogP ]:
4.63110

Related Compounds

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