Ridaifen-B

Ridaifen-B (RID-B) is a potent antagonist of estrogen receptor α (ERα) with IC50 of 52.4 nM, a tamoxifen (HY-13757A) derivative[1]. Ridaifen-B is a high affinity, selective, inverse agonist at CB2 receptor (Ki=43.7 nM) over 17 folds CB1 receptor (Ki=732 nM). Ridaifen-B modulates G-protein (IC50=300 nM) and adenylyl cyclase activity with potency values predicted by CB2 affinity (IC50=134 nM). Ridaifen-B has anti-inflammatory, anti-cancer, and anti-osteoclastogenic effects[1][3].

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

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

ERRα:52.4 nM (IC50)

CB2:43.7 nM (Ki)

CB1:732 nM (Ki)

Ridaifen-B (0-4 μM; 4-24 hours) damages the Jurkat cells in a dose-dependent manner within 4 hours, the IC50 rate is 4 μM. In a longer time, Ridaifen-B also injures Jurkat cells in a dose-dependent manner, similar to the previous results obtained with short-term (4-h), and the IC50 rate is about 0.4 μM[1]. Ridaifen-B (0-4 μM; 4-24 hours) induces cell apoptosis, it activates Caspase-3 in a time-dependent manner, as well as cleaved pro-Caspase-3 to active caspase-3 in ER-negative Jurkat cells[1]. Ridaifen-B (300 nM-1 μM) co-incubates with LPS significantly decreases the Emax of NO production to 19.4 μM, 22.0 μM, and 18.2 μM, respectively in RAW264.7 murine macrophages[1]. Ridaifen-B acts as an inverse agonist at CB2 receptors for modulation of G-protein activity. The potency of RID-B to modulate G-protein activation is examined by employing a non-hydrolyzable radioactive analogue of GTP, [35S]GTPγS, which hinds to G-proteins irreversibly when activated. The CB2 agonist CP-55,940 increases G-protein activation with an EC50 of 2.3 nM. However, RID-B decreases G-protein activation with an IC50 of 300 nM[2]. Consistent with modulation of G-protein activity, RID-B increases adenylyl cyclase activity in a concentration-dependent manner, elevating cAMP levels with an Imax of 398% and a potency (IC50) of 134 nM[2]. Cell Viability Assay[1] Cell Line: Jurkat cells Concentration: 0-4 μM Incubation Time: 4 hours; 24 hours Result: Damaged cell cell viability in both short- and long- term treatment. Apoptosis Analysis[1] Cell Line: Jurkat cells Concentration: 4 μM Incubation Time: 24 hours Result: Induced jurkat cells apoptosis.

[1]. Wen-zhi Guo, et al. Search for novel anti-tumor agents from ridaifens using JFCR39, a panel of human cancer cell lines. Biol Pharm Bull

[2]. Yukitoshi Nagahara, et al.Novel tamoxifen derivative Ridaifen-B induces Bcl-2 independent autophagy without estrogen receptor involvement. Biochem Biophys Res Commun. 2013 Jun 14;435(4):657-63.

[3]. Lirit N Franks, et al. The tamoxifen derivative ridaifen-B is a high affinity selective CB 2 receptor inverse agonist exhibiting anti-inflammatory and anti-osteoclastogenic effects. Toxicol Appl Pharmacol. 2018 Aug 15;353:31-42.