SB-423562

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Chemical Structure| 351490-27-2 同义名 : -
CAS号 : 351490-27-2
货号 : A1149674
分子式 : C26H32N2O4
纯度 : 99%+
分子量 : 436.54
MDL号 : MFCD19443794
存储条件：

Pure form Keep in dark place, sealed in dry, room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(9.16 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
描述 Parathyroid hormone (PTH) plays an essential role in calcium homeostasis by regulating bone resorption, renal calcium excretion, and intestinal calcium absorption. SB-423562 is a novel, short-acting antagonist for calcium-sensing receptor (CaR) that can induce transient PTH release from parathyroid gland. SB-423562 showed a potent in vitro inhibition of CaR-mediated signaling in HEK-293 cells transfected with human CaR (IC50 = 73nM). In rats, SB-423562 was cleared rapidly (89 mL/min/kg) following the i.v. administration and exhibited a short half-life of 0.23h. In preclinical animal models, systemic treatment of SB-423562 following oral administration did not sufficiently induce PTH release due to the poor intestinal absorption and high hepatic extraction of SB-423562. The administration of SB-423557, the ethyl ester precursor of SB-423562, at 15 and 50mg/kg dose-dependently and transiently increased the circulating level of endogenous PTH in rats as compared to the vehicle-treated controls. SB-423557 treatment also resulted in a transient and significant dose-dependent rise (∼10%) in serum Ca2+ at 1 and 2 h post-dose. The transient upregulation of plasma PTH was also observed in dogs (25mg/kg) and monkeys (50mg/kg) following oral administration of SB-423557. The oral administration of SB-423557 (50mg/kg) in ovariectomized rats for 12 weeks significantly increased the bone mineral density (BMD) in lumbar spine, the trabecular BMD of proximal tibia and the endocortical bone formation rate of distal tibia as compared with the controls[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.29mL

0.46mL

0.23mL

11.45mL

2.29mL

1.15mL

22.91mL

4.58mL

2.29mL
参考文献

[1]Kumar S, Matheny CJ, et al. An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone. 2010 Feb;46(2):534-42.

[2]Kumar S, Matheny CJ, Hoffman SJ, Marquis RW, Schultz M, Liang X, Vasko JA, Stroup GB, Vaden VR, Haley H, Fox J, DelMar EG, Nemeth EF, Lago AM, Callahan JF, Bhatnagar P, Huffman WF, Gowen M, Yi B, Danoff TM, Fitzpatrick LA. An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone. 2010 Feb;46(2):534-42.