VU-0357121

VU-0357121 is a positive allosteric modulator of mGlu5 receptors (EC50 = 33 nM). Mutagenesis studies indicate that VU-0357121 and related analogues bind to a yet uncharacterized allosteric site on mGlu(5), distinct from CPPHA, yet share a functional interaction with the MPEP site.

Product information

CAS Number: 433967-28-3

Molecular Weight: 305.32

Formula: C17H17F2NO2

Synonym:

VU 0357121

VU0357121

VU-0357121

Chemical Name: 4-Butoxy-N-(2,4-difluorophenyl)benzamide

Smiles: CCCCOC1C=CC(=CC=1)C(=O)NC1=CC=C(F)C=C1F

InChiKey: AHCYOTLTLQTPSU-UHFFFAOYSA-N

InChi: InChI=1S/C17H17F2NO2/c1-2-3-10-22-14-7-4-12(5-8-14)17(21)20-16-9-6-13(18)11-15(16)19/h4-9,11H,2-3,10H2,1H3,(H,20,21)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 61 mg/mL(199.79 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:

VU-0357121 has the ability to enhance glutamate sensitivity of mGlu5 is likely due to the interaction at a site on the receptor distinct from the MPEP binding site. VU-0357121 does not bind at the MPEP allosteric site of mGlu5, thus does not possess mGlu5 NAM activity. The A809V/rmGlu5 mutation inhibited the ability of VU-0357121 to shift the glutamate concentration response curve, whereas the response to VU-0357121 is not altered by the F585I/rmGlu5 mutation. VU-0357121 shows weaker cooperativity in the Ca2+ mobilization assay in the low-expressing HEK293A-mGlu5 cell line.

References:

1. Rodriguez AL, Tarr JC, Zhou Y, Williams R, Gregory KJ, Bridges TM, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Identification of a glycine sulfonamide based non-MPEP site positive allosteric potentiator (PAM) of mGlu(5). 2012 Dec 17 [updated 2013 Mar 22]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK154499/ PubMed PMID: 24027804.
2. Hammond AS, Rodriguez AL, Townsend SD, Niswender CM, Gregory KJ, Lindsley CW, Conn PJ. Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. ACS Chem Neurosci. 2010 Oct 20;1(10):702-716. Epub 2010 Aug 19. PubMed PMID: 20981342; PubMed Central PMCID: PMC2957851.

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