CPPHA

• CAT Number: I004605
• CAS Number: 693288-97-0
• Molecular Formula: C22H15ClN2O4
• Molecular Weight: 406.82
• Purity: ≥95%
• Synonyms: N-[4-chloro-2-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]-2-hydroxybenzamide
• InChI: InChI=1S/C22H15ClN2O4/c23-14-9-10-18(24-20(27)17-7-3-4-8-19(17)26)13(11-14)12-25-21(28)15-5-1-2-6-16(15)22(25)29/h1-11,26H,12H2,(H,24,27)
• InChIKey: UFOUABRZSDGGAZ-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C(=O)N(C2=O)CC3=C(C=CC(=C3)Cl)NC(=O)C4=CC=CC=C4O

CPPHA is potent and selective positive allosteric modulator (PAM) of the mGluR5 and mGluR1 (metabotropic glutamate receptor). CPPHA can potentiate responses of mGluR5 and mGluR1 to activation of these receptors. CPPHA is developed for the research of central nervous system disorders[1][2].
CPPHA alone has no agonist activity[1].
CPPHA causes concentration-dependent potentiation of the response of human mGluR5 CHO cells to agonists[1].
CPPHA potentiates threshold response to glutamate in fluorometric Ca2+ assays 7- to 8-fold with EC50 values in the 400 to 800 nM range[1].
CPPHA (20 μM; 15 minutes) potentiates the response to a subthreshold concentration of DHPG (HY-12598A) on ERK and cyclic-AMP responsive element-binding protein (CREB) activity, as well as NMDA receptor subunit NR1 phosphorylation in cortical and hippocampal slices[3].

Reference

[1]. O’Brien JA, et al. A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J Pharmacol Exp Ther. 2004 May;309(2):568-77.
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[2]. N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors. Mol Pharmacol. 2008 Mar;73(3):909-18.
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[3]. Liu F, et al. The effect of mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices. Eur J Pharmacol. 2006 May 1;536(3):262-8.
 [Content Brief]

[4]. Zhang Y, et al. Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J Pharmacol Exp Ther. 2005 Dec;315(3):1212-9.
 [Content Brief]