Cannabis Compound Database: Showing Compound Card for Cannabigerovarin (CDB000006)

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Record Information

Version

1.0

Created at

2020-03-19 00:34:54 UTC

Updated at

2020-11-18 16:35:09 UTC

CannabisDB ID

CDB000006

Secondary Accession Numbers

Not Available

Cannabis Compound Identification

Common Name

Cannabigerovarin

Description

Cannabidivarin (CBDV) is a non-psychoactive cannabinoid found within medical Cannabis. It is one of over 100 cannabinoids identified from the Cannabis plants that can modulate the physiological activity of cannabis, or marijuana (PubMed ID 23408483). CBDV is the C3 analogue of cannabidiol (CBD). Notably, both cannabidiol and CBDV have demonstrated anticonvulsant activity in animal and human models and are demonstrating promising clinical trial results (PMID: 22970845 ; PMID: 25029033 ; PMID: 29290836 ; PMID: 29588939 ). Other cannabinoids with some evidence of anti-epileptic activity include Tetrahydrocannabivarin (THCV) and Œî9-tetrahydrocannabinolic acid. While the primary components of cannabis, CBD and THC, have been shown to modulate many of their physiological effects through their binding to the cannabinoid-1 (CB1R) and cannabinoid-2 (CB2R) receptors, the investigational cannabinoids with anticonvulsant action mostly use mechanisms that do not involve these two endocannabinoid receptors. The anti-epileptic activity of CBD and CBDV is thought to be modulated by their effects on transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor, which is a member of a large family of ion channels that are involved in the onset and progression of several types of epilepsy. CBD and CBDV have been shown to dose-dependently activate and then desensitize TRPV1 as well as TRPV2 and TRPA1 channels (PMID 25029033 ; PMID: 29842819 ; PMID: 21175579 ). Desensitization of these ion channels is a potential mechanism by which these molecules cause a reduction of neuronal hyperexcitability that contributes to epileptic activity and seizures. CBDV has also been shown to inhibit the activity of diacylglycerol (DAG) lipase-Œ±, the primary enzyme responsible for the synthesis of the endocannabinoid, 2-arachidonoylglycerol (2-AG) (PMID: 24282673 ; PMID: 14610053 ). The clinical implications of this are unclear however, as this interaction has not been shown to affect CBDV's anticonvulsant activity. Cannabidivarin is being actively developed by GW Pharmaceuticals as the experimental compound GWP42006 as it has "shown the ability to treat seizures in pre-clinical models of epilepsy with significantly fewer side effects than currently approved anti-epileptic drugs". Unfortunately, as of February 2018, GW Pharmaceuticals announced that their Phase 2a placebo-controlled study of CBDV for focal seizure did not reach its primary endpoints. They will continue to study its use in epilepsy, however, and are expanding their investigations to include its potential use in Autism Spectrum Disorder, Rett syndrome and Fragile X among others. In October 2017 CBDV was given orphan designation by the European Medicines Agency for use in Rett Syndrome and again in February 2018 for treatment of Fragile X Syndrome.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Not Available

Chemical Formula

C₁₉H₂₈O₂

Average Molecular Weight

288.43

Monoisotopic Molecular Weight

288.2089

IUPAC Name

2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-5-propylbenzene-1,3-diol

Traditional Name

2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-5-propylbenzene-1,3-diol

CAS Registry Number

55824-11-8

SMILES

CCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1

InChI Identifier

InChI=1S/C19H28O2/c1-5-7-16-12-18(20)17(19(21)13-16)11-10-15(4)9-6-8-14(2)3/h8,10,12-13,20-21H,5-7,9,11H2,1-4H3/b15-10+

InChI Key

YJYIDZLGVYOPGU-XNTDXEJSSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as aromatic monoterpenoids. These are monoterpenoids containing at least one aromatic ring.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Prenol lipids

Sub Class

Monoterpenoids

Direct Parent

Aromatic monoterpenoids

Alternative Parents

Substituents

Monocyclic monoterpenoid
Aromatic monoterpenoid
Phenylpropane
Resorcinol
1-hydroxy-4-unsubstituted benzenoid
1-hydroxy-2-unsubstituted benzenoid
Phenol
Benzenoid
Monocyclic benzene moiety
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Ontology

Not Available

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
logP	Not Available	Not Available

Predicted Properties

Property	Value	Source
logP	5.91	ALOGPS
logP	6.16	ChemAxon
logS	-4.6	ALOGPS
pKa (Strongest Acidic)	9.16	ChemAxon
pKa (Strongest Basic)	-5.7	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	40.46 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	92.31 m³·mol⁻¹	ChemAxon
Polarizability	35.2 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

EI-MS/GC-MS

Type	Description	Splash Key	View
Predicted GC-MS	Cannabigerovarin, 1 TMS, Predicted GC-MS Spectrum - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Cannabigerovarin, 2 TMS, Predicted GC-MS Spectrum - 70eV, Positive	Not Available	Spectrum

MS/MS

Type	Description	Splash Key	View
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available	2020-06-30	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available	2020-06-30	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available	2020-06-30	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available	2020-06-30	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available	2020-06-30	View Spectrum
Predicted MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available	2020-06-30	View Spectrum

NMR

Not Available

Pathways

Not Available

Protein Targets

Enzymes

Protein Name	Gene Name	Locus	Uniprot ID	Details
Sn1-specific diacylglycerol lipase alpha	DAGLA	11q12.2	Q9Y4D2	details

Transporters

Protein Name	Gene Name	Locus	Uniprot ID	Details
Transient receptor potential cation channel subfamily V member 1	TRPV1	17p13.2	Q8NER1	details
Transient receptor potential cation channel subfamily V member 2	TRPV2	17p11.2	Q9Y5S1	details
Transient receptor potential cation channel subfamily A member 1	TRPA1	8q13	O75762	details

Metal Bindings

Not Available

Receptors

Protein Name	Gene Name	Locus	Uniprot ID	Details
Transient receptor potential cation channel subfamily V member 1	TRPV1	17p13.2	Q8NER1	details
Transient receptor potential cation channel subfamily V member 2	TRPV2	17p11.2	Q9Y5S1	details
Transient receptor potential cation channel subfamily A member 1	TRPA1	8q13	O75762	details

Transcriptional Factors

Not Available

Concentrations Data

Not Available

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

59444407

PDB ID

Not Available

ChEBI ID

Not Available

References

General References

Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y, Futamura T, Duncan M, Stott CG, Stephens GJ, Williams CM, Whalley BJ: Cannabidivarin is anticonvulsant in mouse and rat. Br J Pharmacol. 2012 Dec;167(8):1629-42. doi: 10.1111/j.1476-5381.2012.02207.x. [PubMed:22970845 ]
Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, Di Marzo V, Stephens GJ: Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014 Nov 19;5(11):1131-41. doi: 10.1021/cn5000524. Epub 2014 Jul 29. [PubMed:25029033 ]
Capasso A: Do Cannabinoids Confer Neuroprotection Against Epilepsy? An Overview. Open Neurol J. 2017 Dec 18;11:61-73. doi: 10.2174/1874205X01711010061. eCollection 2017. [PubMed:29290836 ]
Morano A, Cifelli P, Nencini P, Antonilli L, Fattouch J, Ruffolo G, Roseti C, Aronica E, Limatola C, Di Bonaventura C, Palma E, Giallonardo AT: Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin. Epilepsia Open. 2016 Sep 19;1(3-4):145-151. doi: 10.1002/epi4.12015. eCollection 2016 Dec. [PubMed:29588939 ]
Ruzic Zecevic D, Folic M, Tantoush Z, Radovanovic M, Babic G, Jankovic SM: Investigational cannabinoids in seizure disorders, what have we learned thus far? Expert Opin Investig Drugs. 2018 Jun;27(6):535-541. doi: 10.1080/13543784.2018.1482275. Epub 2018 Jun 6. [PubMed:29842819 ]
De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V: Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011 Aug;163(7):1479-94. doi: 10.1111/j.1476-5381.2010.01166.x. [PubMed:21175579 ]
Amada N, Yamasaki Y, Williams CM, Whalley BJ: Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. PeerJ. 2013 Nov 21;1:e214. doi: 10.7717/peerj.214. eCollection 2013. [PubMed:24282673 ]
Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P: Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol. 2003 Nov 10;163(3):463-8. doi: 10.1083/jcb.200305129. [PubMed:14610053 ]

Enzymes

Enzyme Details

1. Sn1-specific diacylglycerol lipase alpha

General function:: Involved in triglyceride lipase activity
Specific function:: Catalyzes the hydrolysis of diacylglycerol (DAG) to 2- arachidonoyl-glycerol (2-AG), the most abundant endocannabinoid in tissues. Required for axonal growth during development and for retrograde synaptic signaling at mature synapses
Gene Name:: DAGLA
Uniprot ID:: Q9Y4D2
Molecular weight:: 114950.7

Transporters

Enzyme Details

1. Transient receptor potential cation channel subfamily V member 1

General function:: Involved in ion channel activity
Specific function:: Receptor-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL
Gene Name:: TRPV1
Uniprot ID:: Q8NER1
Molecular weight:: 94955.3

Enzyme Details

2. Transient receptor potential cation channel subfamily V member 2

General function:: Involved in ion channel activity
Specific function:: Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH
Gene Name:: TRPV2
Uniprot ID:: Q9Y5S1
Molecular weight:: 85980.3

Enzyme Details

3. Transient receptor potential cation channel subfamily A member 1

General function:: Not Available
Specific function:: Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system
Gene Name:: TRPA1
Uniprot ID:: O75762
Molecular weight:: 127485.8

Showing Compound Card for Cannabigerovarin (CDB000006)

Structure for CDB000006 (Cannabigerovarin)

Enzymes

Transporters