MedChemExpress LLC (MCE)

MedChemExpress - Model Darifenacin - 133099-04-4

Darifenacin (UK-88525) is a selective and orally active M3 muscarinic receptor (M3R) antagonist with a pKi of 8.9. Darifenacin binds >20-fold more specifically to M3R than to other muscarinic receptors. Darifenacin can be used in the study of urinary incontinence and other symptoms of overactive bladder. Darifenacin inhibits tumor growth in colorectal cancer cells and has anti-tumor effects[1][2][3][4][5][6].

Darifenacin

MCE China：Darifenacin

Brand：MedChemExpress (MCE)

Cat. No.HY-A0033

CAS：133099-04-4

Synonyms：UK-88525

Purity：99.81%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Darifenacin (UK-88525) is a selective and orally active M3 muscarinic receptor (M3R) antagonist with a pKi of 8.9. Darifenacin binds >20-fold more specifically to M3R than to other muscarinic receptors. Darifenacin can be used in the study of urinary incontinence and other symptoms of overactive bladder. Darifenacin inhibits tumor growth in colorectal cancer cells and has anti-tumor effects.

In Vitro：Darifenacin (0.01-100 μM; 5 min) inhibits the Kv currents in concentration-dependent manners with an IC50 value of 0.34 μM and a Hill coefficient of 0.84 in coronary arterial smooth muscle cells[2]. Darifenacin (0.01-10 μM; 1-48 h) inhibits cell viability, invasion and MMP-1 expression in colorectal cancer cells, and inhibits the phosphorylation of p38, ERK1/2 and Akt induced by muscarinic acetylcholine [3].

In Vivo：Darifenacin (2.5 mg/kg; Intraperitoneal injection; 42 days) has an antitumor effect in a xenograft mouse model of colorectal cancer[3]. Darifenacin (0.1 mg/kg; Intravenous injection; Single dose) decreases the afferent activity of bladder Aδ and C fibers in female rats[4]. Darifenacin (3 mg/kg/day; Subcutaneous osmotic pump; 14 weeks) increases the severity of liver damage caused by Azoxymethane (HY-111375)[5].

IC50 & Target：mAChR3 ERK1 ERK2 MMP-1

References：

[1]. Hegde SS, et al. Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol, 1997, 120(8), 1409-1418. [Content Brief]

[2]. Seo MS, et al. Suppression of voltage-gated K+ channels by darifenacin in coronary arterial smooth muscle cells. Eur J Pharmacol. 2021 Jan 15;891:173707. [Content Brief]

[3]. Hering NA, et al. Blockage of Cholinergic Signaling via Muscarinic Acetylcholine Receptor 3 Inhibits Tumor Growth in Human Colorectal Adenocarcinoma. Cancers (Basel). 2021 Jun 28;13(13):3220. [Content Brief]

[4]. Iijima K, et al. Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve. Eur Urol, 2007, 52(3), 842-847. [Content Brief]

[5]. Khurana S, et al. Effects of modulating M3 muscarinic receptor activity on azoxymethane-induced liver injury in mice. Biochem Pharmacol. 2013 Jul 15;86(2):329-38. [Content Brief]

[6]. Yamada S, et al. In vivo demonstration of M3 muscarinic receptor subtype selectivity of darifenacin in mice. Life Sci. 2006 Dec 14;80(2):127-32. [Content Brief]

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