| Description | CTEP (RO 4956371) (RO4956371) is a novel, long-acting, orally bioavailable allosteric antagonist of mGlu5 receptor with IC50 of 2.2 nM, shows >1000-fold selectivity over other mGlu receptors. |
| In vitro | CTEP 在稳定表达人类mGlu5的HEK293细胞中，通过IC50为11.4 nM抑制quisqualate诱导的Ca2+动员以及通过IC50为6.4 nM抑制[3H]IP积累。CTEP还以IC50为40.1 nM约50%地抑制稳定表达人类mGlu5的HEK293细胞中人类mGlu5的构成活性。[1] |
| In vivo | CTEP在0.1 mg/kg和0.3 mg/kg的剂量下对小鼠的焦虑治疗显示出显著活性。在大鼠的Vogel冲突饮水测试中，0.3 mg/kg和1.0 mg/kg的剂量显著增加饮水时间，而更低剂量则无效果。CTEP（口服）的半衰期为18小时，基于血浆和全脑匀浆中总化合物浓度的B/P比值为2.6。单次口服4.5和8.7 mg/kg的CTEP微悬浮液（盐水/Tween载体）给成年C57BL/6小鼠后，化合物迅速吸收，大约30分钟后达到接近最大暴露。成年小鼠连续每48小时口服2 mg/kg的CTEP治疗2个月，最低CTEP大脑暴露浓度达到240 ng/g。CTEP完全置换已知表达mGlu5的小鼠大脑区域中的[3H]ABP688，产生平均化合物浓度为77.5 ng/g（在全脑匀浆中测量）的剂量可实现50%置换。[1] CTEP（2 mg/kg p.o. bid）在小鼠体内每48小时实现不间断的mGlu5占用。CTEP（2 mg/kg p.o.）治疗纠正了Fmr1基因敲除小鼠中海马区长时程抑制、过度蛋白质合成和声诱惊厥的问题。[2] |
| Target activity | mGlu5:2.2 nM |
| Synonyms | mGluR5 inhibitor, RO 4956371 |
| molecular weight | 391.77 |
| Molecular formula | C19H13ClF3N3O |
| CAS | 871362-31-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: 10 mg/mL (25.52 mM) DMSO: 65 mg/mL (165.91 mM), Sonication is recommended. |
| References | 1. Lindemann L, et al. J Pharmacol Exp Ther, 2011, 339(2), 474-486. 2. Michalon A, et al. Neuron, 2012, 74(1), 49-56. |