PHCCC | CAS#179068-02-1 | mGluR4 modulator

MedKoo Cat#: 526717 | Name: PHCCC

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PHCCC is a positive allosteric modulator of mGluR4. PHCCC exhibits proconvulsant action in three models of epileptic seizures in immature rats. PHCCC reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors. PHCCC showed neuroprotection against betaAP- and NMDA-toxicity in mixed cultures of mouse cortical neurons. This neuroprotection was additive to that induced by the highly efficacious mGluR1 antagonist CPCCOEt and was blocked by MSOP, a group-III mGluR antagonist. Our data provide evidence for a novel pharmacological site on mGluR4, which may be used as a target-site for therapeutics.

Chemical Structure

PHCCC

CAS#179068-02-1

Theoretical Analysis

MedKoo Cat#: 526717

Name: PHCCC

CAS#: 179068-02-1

Chemical Formula: C17H14N2O3

Exact Mass: 294.1004

Molecular Weight: 294.31

Elemental Analysis: C, 69.38; H, 4.79; N, 9.52; O, 16.31

Price and Availability

Size	Price	Availability
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,250.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 3,850.00	2 Weeks
5g	USD 5,950.00	2 Weeks

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Synonym

PHCCC

IUPAC/Chemical Name

(E)-7-(hydroxyimino)-N-phenyl-7,7a-dihydrocyclopropa[b]chromene-1a(1H)-carboxamide

InChi Key

FPXPIEZPAXSELW-CYVLTUHYSA-N

InChi Code

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-

SMILES Code

O=C(C1(C2)C2/C(C3=C(O1)C=CC=C3)=N\O)NC4=CC=CC=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PHCCC is a Group I mGluR antagonist with an IC50 of 3 μM.

In vitro activity:

The group I metabotropic glutamate receptor (mGluR) antagonist, PHCCC, significantly reduced the amplitude of [Ca2+]i transients evoked by a 20 pulse (20 Hz) train of electrical stimuli in L-Glu responsive neurons. This stimulus is known to induce slow synaptic depolarizations. Further, some neurons that had PHCCC sensitive [Ca2+]i transients were calb immunoreactive and received vGluT2 varicosities. Reference: Front Neurosci. 2019 May 1;13:426. https://pubmed.ncbi.nlm.nih.gov/31118881/

In vivo activity:

This study tested for the ability of PHCCC to reverse motor deficits in a reserpine-induced akinesia rodent model of PD. As shown in Fig. 6, PHCCC produced a significant increase in locomotor activity, whereas vehicle or CPCCOEt treatment had no effect under the same conditions. Taken together, these findings suggest that PHCCC is a positive allosteric modulator of mGluR4 in both recombinant and native systems. The in vivo antiparkinsonian actions of PHCCC lend further support to the hypothesis that activation of mGluR4 represents a viable therapeutic approach for the treatment of PD and provides evidence that allosteric potentiators of the group III mGluRs have therapeutic potential. Reference: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13668-73. https://pubmed.ncbi.nlm.nih.gov/14593202/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	21.0	71.23

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 294.31 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Swaminathan M, Hill-Yardin EL, Bornstein JC, Foong JPP. Endogenous Glutamate Excites Myenteric Calbindin Neurons by Activating Group I Metabotropic Glutamate Receptors in the Mouse Colon. Front Neurosci. 2019 May 1;13:426. doi: 10.3389/fnins.2019.00426. PMID: 31118881; PMCID: PMC6504831. 2. Gammon JM, Adapa AR, Jewell CM. Control of autoimmune inflammation using liposomes to deliver positive allosteric modulators of metabotropic glutamate receptors. J Biomed Mater Res A. 2017 Nov;105(11):2977-2985. doi: 10.1002/jbm.a.36151. Epub 2017 Jul 14. PMID: 28646511. 3. Szczurowska E, Mareš P. 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. doi: 10.33549/physiolres.932336. Epub 2012 Oct 25. PMID: 23098651. 4. Marino MJ, Williams DL Jr, O'Brien JA, Valenti O, McDonald TP, Clements MK, Wang R, DiLella AG, Hess JF, Kinney GG, Conn PJ. 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. doi: 10.1073/pnas.1835724100. Epub 2003 Oct 30. PMID: 14593202; PMCID: PMC263871.

In vitro protocol:

In vivo protocol:

1. Szczurowska E, Mareš P. 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. doi: 10.33549/physiolres.932336. Epub 2012 Oct 25. PMID: 23098651. 2. Marino MJ, Williams DL Jr, O'Brien JA, Valenti O, McDonald TP, Clements MK, Wang R, DiLella AG, Hess JF, Kinney GG, Conn PJ. 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. doi: 10.1073/pnas.1835724100. Epub 2003 Oct 30. PMID: 14593202; PMCID: PMC263871.

1: Szczurowska E, Mareš P. 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. Epub 2012 Oct 25. PubMed PMID: 23098651. 2: Williams R, Zhou Y, Niswender CM, Luo Q, Conn PJ, Lindsley CW, Hopkins CR. Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4. ACS Chem Neurosci. 2010 Jun 16;1(6):411-419. PubMed PMID: 20582156; PubMed Central PMCID: PMC2889702. 3: Kłak K, Pałucha A, Brański P, Sowa M, Pilc A. Combined administration of PHCCC, a positive allosteric modulator of mGlu4 receptors and ACPT-I, mGlu III receptor agonist evokes antidepressant-like effects in rats. Amino Acids. 2007 Feb;32(2):169-72. Epub 2006 Aug 2. PubMed PMID: 16868652. 4: Canudas AM, Di Giorgi-Gerevini V, Iacovelli L, Nano G, D'Onofrio M, Arcella A, Giangaspero F, Busceti C, Ricci-Vitiani L, Battaglia G, Nicoletti F, Melchiorri D. PHCCC, a specific enhancer of type 4 metabotropic glutamate receptors, reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors. J Neurosci. 2004 Nov 17;24(46):10343-52. PubMed PMID: 15548648. 5: Stachowicz K, Kłak K, Kłodzińska A, Chojnacka-Wojcik E, Pilc A. Anxiolytic-like effects of PHCCC, an allosteric modulator of mGlu4 receptors, in rats. Eur J Pharmacol. 2004 Sep 13;498(1-3):153-6. PubMed PMID: 15363989. 6: Maj M, Bruno V, Dragic Z, Yamamoto R, Battaglia G, Inderbitzin W, Stoehr N, Stein T, Gasparini F, Vranesic I, Kuhn R, Nicoletti F, Flor PJ. (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 2003 Dec;45(7):895-906. PubMed PMID: 14573382.