CTEP

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CTEP (RO4956371) 是一种新型、长效、口服生物可利用的 mGlu5 受体变构拮抗剂，IC50 为 2.2 nM，选择性是其他 mGlu 受体的 1000 倍以上。

CTEP, also known as RO4956371, is a potent, long-acting, orally bioavailable allosteric antagonist of mGlu5 receptor with IC50 of 2.2 nM. CTEP binds mGlu5 with low nanomolar affinity and shows >1000-fold selectivity when tested against 103 targets, including all known mGlu receptors. CTEP penetrates the brain with a brain/plasma ratio of 2.6 and displaces the tracer ABP688 in vivo in mice from brain regions expressing mGlu5 with an average ED(50) equivalent to a drug concentration of 77.5 ng/g in brain tissue.

CTEP (RO 4956371) inhibits quisqualate-induced Ca2+?mobilization with an IC50 of 11.4 nM and [3H]IP accumulation with an IC50 of 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 IC50 of 40.1 nM in HEK293 cells stably expressing human mGlu5.

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.? 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.

RO4956371 | RO-4956371 | RO 4956371 | CTEP

Endocrinology/Hormones

5-HT Receptor

mGluR5

Neurological Disease

——

871362-31-1

391.77

C19H13ClF3N3O

>98% (HPLC)

DMSO : ≥ 100 mg/mL. 255.25 mM; H2O : < 0.1 mg/mL

CC1=NC(C#CC2=CC=NC(Cl)=C2)=C(C)N1C1=CC=C(OC(F)(F)F)C=C1

2-chloro-4-[2-[2,5-dimethyl-1-[4-(trifluoromethoxy)phenyl]imidazol-4-yl]ethynyl]pyridine

(-20℃)

With Ice Pack

≥ 2 years