Sutherland M Kung, Brady H, Gayo-Fung L M, Leisten J, Lipps S G, McKie J A, O'Leary E, Patnaik N, Anderson D W, Bhagwat S S, Stein B
Celgene Corp., 4550 Towne Centre Court, San Diego, CA 92121, USA.
Calcif Tissue Int. 2003 Jun;72(6):710-6. doi: 10.1007/s00223-002-1029-2.
We describe here the activity of a novel selective estrogen receptor modulator, SP500263. When given to adult ovariectomized (OVX) rats for 28 days at doses of 0.3, 1, or 3 mg/kg/day, we found that SP500263 partially protected against OVX-induced loss of bone mineral content in the distal ends of femurs and in the whole bone. SP500263 also antagonized the OVX-induced increase in body weight. However, unlike 17beta-estradiol, SP500263 at efficacious doses did not prevent the OVX-induced loss in uterine wet weight. A small but significant effect on uterine wet weight was noted with raloxifene dosed at 1 mg/kg. As expected, SP500263 but not raloxifene acted as an estrogen antagonist on the uterus in adult rats when administered for 7 days at 30 mg/kg/day. Finally, SP500263 had no statistically significant effects on total serum cholesterol and serum triglycerides in OVX rats treated for 28 days. Raloxifene had no significant effects on body weight, bone mineral content, and serum cholesterol or triglycerides in the OVX-rat model. In summary, SP500263 is a new orally active SERM that acts in rats as an estrogen agonist on bone without causing uterine stimulatory effects.
我们在此描述一种新型选择性雌激素受体调节剂SP500263的活性。当以0.3、1或3毫克/千克/天的剂量给予成年去卵巢（OVX）大鼠28天时，我们发现SP500263可部分预防OVX诱导的股骨远端和整个骨骼骨矿物质含量的损失。SP500263还可拮抗OVX诱导的体重增加。然而，与17β-雌二醇不同，有效剂量的SP500263并不能预防OVX诱导的子宫湿重减轻。给予1毫克/千克的雷洛昔芬对子宫湿重有轻微但显著的影响。正如预期的那样，当以30毫克/千克/天的剂量给药7天时，SP500263而非雷洛昔芬在成年大鼠子宫中表现为雌激素拮抗剂。最后，在接受28天治疗的OVX大鼠中，SP500263对总血清胆固醇和血清甘油三酯没有统计学上的显著影响。在OVX大鼠模型中，雷洛昔芬对体重、骨矿物质含量以及血清胆固醇或甘油三酯没有显著影响。总之，SP500263是一种新型口服活性选择性雌激素受体调节剂，在大鼠中作为骨上的雌激素激动剂起作用，而不会引起子宫刺激作用。
