CTEP Derivative

CTEP Derivative is a potent, selective and orally available mGlu5 negative allosteric modulator with a Kd of 1.1 nM.

Product information

CAS Number: 802906-73-6

Molecular Weight: 325.77

Formula: C18H13ClFN3

Synonym:

Basimglurant

RG7090

Chemical Name: 2-chloro-4-{2-[1-(4-fluorophenyl)-2, 5-dimethyl-1H-imidazol-4-yl]ethynyl}pyridine

Smiles: CC1=C(C#CC2=CC(Cl)=NC=C2)N=C(C)N1C1C=CC(F)=CC=1

InChiKey: UPZWINBEAHDTLA-UHFFFAOYSA-N

InChi: InChI=1S/C18H13ClFN3/c1-12-17(8-3-14-9-10-21-18(19)11-14)22-13(2)23(12)16-6-4-15(20)5-7-16/h4-7,9-11H,1-2H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

[3H]-basimglurant saturation analysis on recombinant human mGlu5 reveals monophasic saturation isotherms with Kd of 1.1 nM. In competition binding experiments on human recombinant mGlu5, CTEP Derivative fully displaces [3H]-MPEP with a Ki of 35.6 nM and [3H]-ABP688 with a Ki of 1.4 nM. In HEK293 cells stably expressing human mGlu5, CTEP Derivative inhibits quisqualate induced Ca2+ mobilization with an IC50 of 7.0 nM and [3H]-inositolphosphate accumulation with an IC50 of 5.9 nM. CTEP Derivative shows similar potencies in radioligand binding and functional assay on human and rodent mGlu5 receptor orthologues.

In Vivo:

CTEP Derivative is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties which are corroborated by its functional magnetic imaging (fMRI) profile, as well as anxiolytic-like and antinociceptive features. It is currently in phase II clinical studies for the treatment of depression and fragile X syndrome. In the Vogel conflict drinking test, CTEP Derivative dose dependently increases the drinking time. The total plasma exposure of efficacious doses of CTEP Derivative ranges from 5 ng/mL (0.03 mg/kg) to 37 ng/mL (0.3 mg/kg).

References:

1. Jaeschke G, et al. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases.
2. Lindemann L, et al. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J Pharmacol Exp Ther. 2015 Apr;353(1):213-33.

Products are for research use only. Not for human use.