Ro 67-4853 

Ro 67-4853 is a positive allosteric modulator (PAM) of mGluR1 (pEC₅₀=7.16 for rmGlu1a receptor). Ro67-4853 exhibits activity at all group I mGlu receptors including hmGlu1, rmGlu1, and rmGlu5. Ro 67-4853 enhances the potency of L-Glu by interacting with the transmembrane domain (TMD) of the receptor. Ro 67-4853 potentiates sensory synaptic responses to repetitive vibrissa stimulation^[1][2][3][4].

Ro67-4853 selectively potentiates responses to the agonist DHPG^[2].
Ro 67-4853 (1 µM) shifts the concentration-response curve (CRC) of glutamate approximately 2-fold, 15-fold, and 4.5-fold to the left respectively in BHK cells stably expressing mGluR1a^[4].
Ro 67-4853 (1 µM) activates p-ERK1/2 in the absence of agonist with a time course of activation peaking at 5 minutes in BHK cells^[4].
Ro 67-4853 (500 nM) potentiates glutamate-induced activation of mGluR1 as assessed by measures of cAMP production. Glutamate increases cAMP accumulation with an EC50 value of 32.08 µM in the absence of Ro 67-4853. The EC50 values for glutamate in the presence of Ro 67-4853 is 2.15 µM. Ro 67-4853 increases basal mGluR1-induced cAMP accumulation and potentiate glutamate-induced cAMP accumulation but have lower potencies at modulating the cAMP response than at regulating ERK1/2 phosphorylation or calcium mobilization^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

325.36

C₁₉H₁₉NO₄

302841-89-0

Solid

White to off-white

CCCCOC(NC(C1C2=CC=CC=C2OC3=CC=CC=C13)=O)=O

Room temperature in continental US; may vary elsewhere.

-20°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)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Knoflach F, et al. Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site [published correction appears in Proc Natl Acad Sci U S A 2001 Dec 18;98(26):15393]. Proc Natl Acad Sci U S A.  [Content Brief]

  [2]. Jiang JY, et al. Extracellular calcium modulates actions of orthosteric and allosteric ligands on metabotropic glutamate receptor 1α. J Biol Chem. 2014;289(3):1649-1661.  [Content Brief]

  [3]. Salt TE, et al. Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator. Neuropharmacology. 2012;62(4):1695-1699.  [Content Brief]

  [4]. Sheffler DJ, et al. Allosteric potentiators of metabotropic glutamate receptor subtype 1a differentially modulate independent signaling pathways in baby hamster kidney cells. Neuropharmacology. 2008;55(4):419-427.  [Content Brief]