Jervine (T3D4083)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-08-29 05:04:40 UTC
Update Date2014-12-24 20:26:38 UTC
Accession NumberT3D4083
Identification
Common NameJervine
ClassSmall Molecule
DescriptionJervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the Veratrum plant genus. Similar to cyclopamine, which also occurs in the Veratrum genus, it is a teratogen implicated in birth defects when consumed by animals during a certain period of their gestation.
Compound Type
  • Amine
  • Ester
  • Ether
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
SynonymsNot Available
Chemical FormulaC27H39NO3
Average Molecular Mass425.604 g/mol
Monoisotopic Mass425.293 g/mol
CAS Registry Number469-59-0
IUPAC Name(1'S,2R,2'R,3R,3aS,5'S,6S,7aR,10'S,11'S)-5'-hydroxy-2',3,6,15'-tetramethyl-3a,4,5,6,7,7a-hexahydro-3H-spiro[furo[3,2-b]pyridine-2,14'-tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁶]heptadecane]-7',15'-dien-17'-one
Traditional Namejervine
SMILES[H][C@@]12C[C@]([H])(C)CN[C@@]1([H])[C@@]([H])(C)[C@@]1(CC[C@]3([H])C(C(=O)[C@@]4([H])[C@@]3([H])CC=C3C[C@@]([H])(O)CC[C@]43C)=C1C)O2
InChI IdentifierInChI=1S/C27H39NO3/c1-14-11-21-24(28-13-14)16(3)27(31-21)10-8-19-20-6-5-17-12-18(29)7-9-26(17,4)23(20)25(30)22(19)15(27)2/h5,14,16,18-21,23-24,28-29H,6-13H2,1-4H3/t14-,16+,18-,19-,20-,21+,23+,24-,26-,27-/m0/s1
InChI KeyInChIKey=CLEXYFLHGFJONT-DNMILWOZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as jerveratrum-type alkaloids. These are steroidal alkaloids with a structure that is based on the jervane ring system. Jerveratrum alkaloids have alkamines with 1-3 oxygen atoms, and occur as such or as monoglycosides.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassSteroidal alkaloids
Direct ParentJerveratrum-type alkaloids
Alternative Parents
Substituents
  • Jerveratrum-type alkaloid
  • Azasteroid
  • Alkaloid or derivatives
  • Piperidine
  • Cyclic alcohol
  • Tetrahydrofuran
  • Ketone
  • Secondary alcohol
  • Dialkyl ether
  • Secondary aliphatic amine
  • Ether
  • Oxacycle
  • Secondary amine
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Organopnictogen compound
  • Amine
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular matrix
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0063 g/LALOGPS
logP3.43ALOGPS
logP3.39ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)18.2ChemAxon
pKa (Strongest Basic)9.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity122.89 m³·mol⁻¹ChemAxon
Polarizability51.03 ųChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a6r-0001900000-c6cd0e861335854cc21b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ab9-3569600000-9f93284c65706877006e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-a471f5794d2332789cd62016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0001900000-b3d40c10be62db9448962016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05fr-0101900000-0d5d5c88891f8215ce042016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0v4j-9414100000-19933bc2b637e92427cf2016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityJervine's biological activity is mediated via its interaction with the 7 pass trans membrane protein smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the hedgehog signaling pathways. With smoothened inhibited, the GLI1 transcription cannot be activated and hedgehog target genes cannot be transcribed. (Wikipedia) It is now known that the teratogenic effects of jervine and cyclopamine are due to their specific inhibition of vertebrate cellular responses to the Hedgehog (Hh) family of secreted growth factors. (1) In cultures with cyclopamine, jervine, or blocking antibody, fungiform papilla numbers doubled on the dorsal tongue with a distribution that essentially eliminated inter-papilla regions, compared with tongues in standard medium or solanidine. (2)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesJervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the Veratrum plant genus.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID10098
ChEMBL IDCHEMBL186779
ChemSpider ID9694
KEGG IDC10811
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkJervine
References
Synthesis ReferenceNot Available
MSDST3D4083.pdf
General References
  1. Chen JK, Taipale J, Cooper MK, Beachy PA: Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 2002 Nov 1;16(21):2743-8. [12414725 ]
  2. Mistretta CM, Liu HX, Gaffield W, MacCallum DK: Cyclopamine and jervine in embryonic rat tongue cultures demonstrate a role for Shh signaling in taste papilla development and patterning: fungiform papillae double in number and form in novel locations in dorsal lingual epithelium. Dev Biol. 2003 Feb 1;254(1):1-18. [12606278 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
General Function:
Transmembrane signaling receptor activity
Specific Function:
Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
Gene Name:
EBP
Uniprot ID:
Q15125
Molecular Weight:
26352.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 50170645
References
  1. Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]
Target Details
2. Sigma non-opioid intracellular receptor 1
General Function:
Opioid receptor activity
Specific Function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular Weight:
25127.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 50170645
References
  1. Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]
Target Details
3. Sonic hedgehog protein
General Function:
Zinc ion binding
Specific Function:
Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO (By similarity).
Gene Name:
SHH
Uniprot ID:
Q15465
Molecular Weight:
49606.685 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.5 uMNot AvailableBindingDB 50170645
References
  1. Mahindroo N, Punchihewa C, Fujii N: Hedgehog-Gli signaling pathway inhibitors as anticancer agents. J Med Chem. 2009 Jul 9;52(13):3829-45. doi: 10.1021/jm801420y. [19309080 ]