PHCCC

Potent group I mGlu antagonist CAS# 179068-02-1

PHCCC

Catalog No. BCC6895----Order now to get a substantial discount!

Product Name & Size Price Stock
PHCCC: 5mg $92 In Stock
PHCCC: 10mg Please Inquire In Stock
PHCCC: 20mg Please Inquire Please Inquire
PHCCC: 50mg Please Inquire Please Inquire
PHCCC: 100mg Please Inquire Please Inquire
PHCCC: 200mg Please Inquire Please Inquire
PHCCC: 500mg Please Inquire Please Inquire
PHCCC: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of PHCCC

Number of papers citing our products

Chemical structure

PHCCC

3D structure

Chemical Properties of PHCCC

Cas No. 179068-02-1 SDF Download SDF
PubChem ID 5866327 Appearance Powder
Formula C17H14N2O3 M.Wt 294.31
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : ≥ 32 mg/mL (108.73 mM)
*"≥" means soluble, but saturation unknown.
Chemical Name (7E)-7-hydroxyimino-N-phenyl-1,7a-dihydrocyclopropa[b]chromene-1a-carboxamide
SMILES C1C2C1(OC3=CC=CC=C3C2=NO)C(=O)NC4=CC=CC=C4
Standard InChIKey FPXPIEZPAXSELW-CYVLTUHYSA-N
Standard InChI InChI=1S/C17H14N2O3/c20-16(18-11-6-2-1-3-7-11)17-10-13(17)15(19-21)12-8-4-5-9-14(12)22-17/h1-9,13,21H,10H2,(H,18,20)/b19-15-
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of PHCCC

DescriptionGroup I metabotropic glutamate receptor antagonist (IC50 ~ 3 μM); 67 times more potent than (S)-4-carboxyphenylglycine. Also a positive allosteric modulator for mGlu4a; potentiates L-AP4-mediated inhibition of striatopallidal synaptic transmission in vitro. Displays antiParkinsonian effects in rats in vivo.

PHCCC Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

PHCCC Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of PHCCC

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.3978 mL 16.9889 mL 33.9778 mL 67.9556 mL 84.9444 mL
5 mM 0.6796 mL 3.3978 mL 6.7956 mL 13.5911 mL 16.9889 mL
10 mM 0.3398 mL 1.6989 mL 3.3978 mL 6.7956 mL 8.4944 mL
50 mM 0.068 mL 0.3398 mL 0.6796 mL 1.3591 mL 1.6989 mL
100 mM 0.034 mL 0.1699 mL 0.3398 mL 0.6796 mL 0.8494 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on PHCCC

PHCCC is a Group I metabotropic glutamate receptor antagonist with EC50 of 6 uM and a positive allosteric modulator of mGluR4. Also as a potent to antagonism for mGluR2 and mGluR8. target: a Group I metabotropic glutamate receptor antagonist EC 50: 6 uM In vitro: PHCCC potentiates L-AP4-mediated inhibition of striatopallidal synaptic transmission in vitro. In vivo: 1, PHCCC produced antiparkinsonian efficacy in the reserpinized rat model means a significant level of glutamate is available for the activation of the therapeutically relevant mGluR4. 2, The reference for animal administration is 10 mg/kg.(i.p) 3,PHCCC augmentes in vivo genetic and pharmacological models of absence seizures in rats.

References:
[1]. Marino MJ et al. Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13668-73. [2]. Maj M et al. (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 2003 Dec;45(7):895-906. [3]. Szczurowska E et al. Positive allosteric modulator of mGluR4 PHCCC exhibits proconvulsant action in three models of epileptic seizures in immature rats. Physiol Res. 2012;61(6):619-28. [4]. Domin H et al. Neuroprotective potential of the group III mGlu receptor agonist ACPT-I in animal models of ischemic stroke: In vitro and in vivo studies. Neuropharmacology. 2016 Mar;102:276-94.

Featured Products
New Products
 

References on PHCCC

PHCCC, a specific enhancer of type 4 metabotropic glutamate receptors, reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors.[Pubmed:15548648]

J Neurosci. 2004 Nov 17;24(46):10343-52.

Exposure of immature rat cerebellar granule cell cultures to the type 4 metabotropic glutamate (mGlu4) receptor enhancer N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) reduced [3H]thymidine incorporation. Its action was sensitive to the growth conditions and was attenuated by two mGlu4 receptor antagonists. An antiproliferative action of PHCCC was also seen in cultures from wild-type, but not mGlu4, knock-out mice. At least in rat cultures, PHCCC was not neurotoxic and enhanced neuritogenesis. Although PHCCC reduced the increase in cAMP formation and phospho-AKT levels induced by forskolin, none of these transduction pathways significantly contributed to the reduction of [3H]thymidine incorporation. Interestingly, PHCCC reduced the expression of Gli-1, a transcription factor that mediates the mitogenic action of Sonic hedgehog. Finally, we treated newborn rats with PHCCC either intracerebrally (infusion of 5 nmol/2 microl in the cerebellar region once every other day) or systemically (5 mg/kg, i.p., once daily) from postnatal days 3-9. Local infusion of PHCCC induced substantial changes in the morphology of the developing cerebellum. In contrast, systemic injection of PHCCC induced only morphological abnormalities of the cerebellar lobule V, which became visible 11 d after the end of the treatment. These data suggest that mGlu4 receptors are involved in the regulation of cerebellar development.

Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4.[Pubmed:20582156]

ACS Chem Neurosci. 2010 Jun 16;1(6):411-419.

This Letter describes a detailed SAR analysis of the mGluR4 positive allosteric modulator, PHCCC. We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes.

Combined administration of PHCCC, a positive allosteric modulator of mGlu4 receptors and ACPT-I, mGlu III receptor agonist evokes antidepressant-like effects in rats.[Pubmed:16868652]

Amino Acids. 2007 Feb;32(2):169-72.

Numerous pharmacological data indicate involvement of glutamate, the major excitatory neurotransmitter in the brain, in the pathophysiology of several neuropsychiatric disorders. It was shown in the preclinical studies that compounds which can reduce the excess of glutamate release (for example group III metabotropic receptors agonists) possess potential therapeutic properties. Thus we focused our interests on (-)-N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), which is a positive allosteric modulator of mGlu4 receptor. We examined the potential antidepressant-like activity of PHCCC after injection into the brain ventricles alone, or together with (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I), a nonselective group III mGlu receptor agonist, using the forced swimming test (FST) in rats. We found that ACPT-I induced a dose dependent antidepressant-like effect in FST, which was blocked by an antagonist of group III mGlu receptors (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). PHCCC injected intracerebroventricular was not effective, however when the compound was administered together with non-effective dose of ACPT-I, a profound antidepressant-like activity in FST was demonstrated. This effect was reversed by CPPG, group III mGlu receptors antagonist. Results of our studies indicate that a combined administration positive allosteric modulation of mGlu4 receptor and agonists of group III mGlu receptors may be a promising target in the future treatment of depressive disorder.

Positive allosteric modulator of mGluR4 PHCCC exhibits proconvulsant action in three models of epileptic seizures in immature rats.[Pubmed:23098651]

Physiol Res. 2012;61(6):619-28. Epub 2012 Oct 25.

The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electro-encephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats.

Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment.[Pubmed:14593202]

Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13668-73.

Parkinson's disease (PD) is a debilitating movement disorder that afflicts >1 million people in North America. Current treatments focused on dopamine-replacement strategies ultimately fail in most patients because of loss of efficacy and severe adverse effects that worsen as the disease progresses. The recent success of surgical approaches suggests that a pharmacological intervention that bypasses the dopamine system and restores balance in the basal ganglia motor circuit may provide an effective treatment strategy. We previously identified the metabotropic glutamate receptor 4 (mGluR4) as a potential drug target and predicted that selective activation of mGluR4 could provide palliative benefit in PD. We now report that N-phenyl-7-(hydroxylimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) is a selective allosteric potentiator of mGluR4. This compound selectively potentiated agonist-induced mGluR4 activity in cultured cells expressing this receptor and did not itself act as an agonist. Furthermore, PHCCC potentiated the effect of l-(+)-2-amino-4-phosphonobutyric acid in inhibiting transmission at the striatopallidal synapse. Modulation of the striatopallidal synapse has been proposed as a potential therapeutic target for PD, in that it may restore balance in the basal ganglia motor circuit. Consistent with this, PHCCC produced a marked reversal of reserpine-induced akinesia in rats. The closely related analogue 7-(hydroxylimino)cyclopropachromen-1a-carboxamide ethyl ester, which does not potentiate mGluR4, had no effect in this model. These results are evidence for in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of mGluR4 may be a useful therapeutic approach to the treatment of PD.

Selective activation of group I metabotropic glutamate receptors upregulates preprodynorphin, substance P, and preproenkephalin mRNA expression in rat dorsal striatum.[Pubmed:11071713]

Synapse. 2001 Jan;39(1):82-94.

Group I metabotropic glutamate receptors (mGluRs) are positively coupled to phosphoinositide hydrolysis through G-proteins and are densely expressed in the medium-sized spiny neurons of striatum. Activation of this group of mGluRs in the striatum produces long-lasting stimulation of behavioral activity. In this study, the role of group I mGluRs in the modulation of neuropeptide mRNA expression in striatal neurons was investigated using a Group I-selective agonist, 3,5-dihydroxyphenylglycine (DHPG) in chronically cannulated rats. Unilateral injections of DHPG into the dorsal striatum (caudoputamen) at behaviorally active doses of 20, 40, and 80 nmol elevated basal levels of preprodynorphin (PPD), substance P (SP), and preproenkephalin (PPE) mRNAs in the injected dorsal striatum as revealed by quantitative in situ hybridization. The elevation of all three mRNAs was dose-dependent and the responsiveness of opioid peptide mRNAs (PPD and PPE) to acute injection of DHPG at each dose surveyed was greater than that of SP mRNA. Induction of the mRNAs was delayed and prolonged as increases in hybridization signal became evident at 2 (SP and PPE) or 3 (PPD) h, reached a peak between 3 and 6 h, and returned to normal levels 24 h after DHPG injection. Coadministration of a Group I-selective antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carbo xamide (PHCCC, 10 nmol), with DHPG markedly attenuated DHPG-stimulated PPD, PPE, and, to a lesser extent, SP expression. Administration of PHCCC alone had no significant effect on basal levels of three mRNA expression in the striatum. This study provides a detailed description of the dose- and time-related alterations in striatonigral PPD/SP and striatopallidal PPE mRNA expression in response to a single injection of the Group I agonist DHPG. Data obtained demonstrate a facilitatory, dynamic regulation of constitutive expression of PPD, SP, and PPE mRNAs by local enhancement of glutamatergic tone on DHPG- and PHCCC-sensitive Group I mGluRs.

Description

PHCCC is a Group I metabotropic glutamate receptor antagonist with EC 50 of 6 uM and a positive allosteric modulator of mGluR4. Also as a potent to antagonism for mGluR2 and mGluR8.

Keywords:

PHCCC,179068-02-1,Natural Products,GluR, buy PHCCC , PHCCC supplier , purchase PHCCC , PHCCC cost , PHCCC manufacturer , order PHCCC , high purity PHCCC

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: