CTEP --- mGlu5 Antagonist

CTEP is a highly potent, selective and orally bioavailable allosteric antagonist of mGlu5 receptor with an IC50 of 2.2 nM. It shows >1000-fold selectivity against 103 targets, including all known mGlu receptors. CTEP can penetrate the brain with a brain/plasma ratio of 2.6. CTEP is active in the stress-induced hyperthermia procedure in mice and the Vogel conflict drinking test in rats with minimal effective doses of 0.1 and 0.3 mg/kg, respectively, reflecting a 30- to 100-fold higher in vivo potency compared with 2-methyl- 6-(phenylethynyl)pyridine (MPEP) and fenobam. CTEP is the first reported mGlu5 inhibitor with both long half-life of approximately 18 h and high oral bioavailability allowing chronic treatment with continuous receptor blockade with one dose every 48 h in adult and newborn animals. Acute CTEP treatment corrects elevated hippocampal long-term depression, protein synthesis, and audiogenic seizures. Chronic treatment that inhibits mGlu5 within a receptor occupancy range of 81% ± 4% rescues cognitive deficits, auditory hypersensitivity, aberrant dendritic spine density, overactive ERK and mTOR signaling, and partially corrects macroorchidism. By enabling long-term treatment through a wide age range, CTEP allows the exploration of the full therapeutic potential of mGlu5 inhibitors for indications requiring chronic receptor inhibition.

Product information

CAS Number: 871362-31-1

Molecular Weight: 391.77

Formula: C19H13ClF3N3O

Synonym:

RO4956371

Chemical Name: 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine

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

InChiKey: GOHCTCOGYKAJLZ-UHFFFAOYSA-N

InChi: InChI=1S/C19H13ClF3N3O/c1-12-17(8-3-14-9-10-24-18(20)11-14)25-13(2)26(12)15-4-6-16(7-5-15)27-19(21,22)23/h4-7,9-11H,1-2H3

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 mM

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:

CTEP was used at 0.03-0.1 µM final concentration in vitro and in cellular assays.

In Vivo:

CTEP was orally dosed to mice at single 0.1-1.0 mg/kg, or with a dose of 2 mg/kg orally every 48 h for 2 months. CTEP was orally dose at 2 mg/kg BID achieves uninterrupted mGlu5 occupancy per 48 hours in mice.

References:

1. Lindemann L, et al. CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic glutamate receptor 5 inhibitor. (2011) J Pharmacol Exp Ther. 339(2):474-86.
2. Michalon A, et al. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. (2012) Neuron. 74(1):49-56.

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

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