CTEP (RO 4956371) is a novel, long-acting, orally bioavailable allosteric antagonist of mGlu5 receptorwith IC₅₀ of 2.2 nM, and shows >1000-fold selectivity over other mGlu receptors.

CTEP (RO 4956371) inhibits quisqualate-induced Ca²⁺ mobilization with an IC₅₀of 11.4 nM and [³H]IP accumulation with an IC₅₀of 6.4 nM in HEK293 cells stably expressing human mGlu5. CTEP (RO 4956371) inhibits the constitutive activity of human mGlu5 by approximately 50% with an IC₅₀of 40.1 nM in HEK293 cells stably expressing human mGlu5^[1].

CTEP (RO 4956371) is significantly active at doses of 0.1 mg/kg and 0.3 mg/kg in treatment of anxiety in mouse. CTEP (RO 4956371) significantly increases drinking time at doses of 0.3 mg/kg and 1.0 mg/kg in the Vogel conflict drinking test in rat, whereas it has no effect at lower doses. The half-life of CTEP (RO 4956371) (oral) is 18 h, and the B/P ratio based on total drug concentrations in plasma and whole brain homogenates is 2.6 in mice. After single oral doses of 4.5 and 8.7 mg/kg CTEP (RO 4956371) formulated as microsuspension in a saline/Tween vehicle administrated to adult C57BL/6 mice is rapidly absorbed and achieves close to maximal exposure after approximately 30 min. Chronic administration in adult mice with a dose of 2 mg/kg p.o. every 48 h for 2 months reaches a minimal CTEP (RO 4956371) brain exposure of 240 ng/g. CTEP (RO 4956371) fully displaces [³H]ABP688 in mouse brain regions known to express mGlu5, and 50% displacement is achieved with doses producing an average compound concentration of 77.5 ng/g measured in whole brain homogenate^[1]. CTEP (RO 4956371) (2 mg/kg, p.o. bid) achieves uninterrupted mGlu5 occupancy per 48 hours in mice. CTEP (RO 4956371) (2 mg/kg, p.o.) treatment corrects elevated hippocampal long-term depression, excessive protein synthesis, and audiogenic seizures in the Fmr1 knockout mouse^[2].

391.77

Solid

C₁₉H₁₃ClF₃N₃O

871362-31-1

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

DMSO : ≥ 100 mg/mL(255.25 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (6.38 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.38 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: 2.5 mg/mL (6.38 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (6.38 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (6.38 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.38 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。