You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-08-29 04:49:26 UTC
Update Date2014-12-24 20:26:36 UTC
Accession NumberT3D4027
Identification
Common Name(S)-Isocorydine
ClassSmall Molecule
Description(S)-Isocorydine is found in cherimoya. (S)-Isocorydine is an alkaloid from Peumus boldus (boldo). (S)-Isocorydine belongs to the family of Aporphines. These are quinoline alkaloids containing the dibenzo[de,g]quinoline ring system.
Compound Type
  • Amine
  • Ether
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
(+)-(S)-Isocorydine
(+)-Isocorydine
(S)-(+)-Isocorydine
1,2,10-Trimethoxy-6a-alpha-Aporphin-11-ol
L-(+)-Isocorydine
S-Artabotrine
S-Luteanine
Chemical FormulaC20H23NO4
Average Molecular Mass341.401 g/mol
Monoisotopic Mass341.163 g/mol
CAS Registry Number475-67-2
IUPAC Name(9S)-4,15,16-trimethoxy-10-methyl-10-azatetracyclo[7.7.1.0²,⁷.0¹³,¹⁷]heptadeca-1(16),2,4,6,13(17),14-hexaen-3-ol
Traditional Name(9S)-4,15,16-trimethoxy-10-methyl-10-azatetracyclo[7.7.1.0²,⁷.0¹³,¹⁷]heptadeca-1(16),2,4,6,13(17),14-hexaen-3-ol
SMILES[H][C@]12CC3=C(C(O)=C(OC)C=C3)C3=C1C(CCN2C)=CC(OC)=C3OC
InChI IdentifierInChI=1S/C20H23NO4/c1-21-8-7-12-10-15(24-3)20(25-4)18-16(12)13(21)9-11-5-6-14(23-2)19(22)17(11)18/h5-6,10,13,22H,7-9H2,1-4H3/t13-/m0/s1
InChI KeyInChIKey=QELDJEKNFOQJOY-ZDUSSCGKSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aporphines. These are quinoline alkaloids containing the dibenzo[de,g]quinoline ring system or a dehydrogenated derivative thereof.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassAporphines
Sub ClassNot Available
Direct ParentAporphines
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point185°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.1 g/LALOGPS
logP2.83ALOGPS
logP2.92ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)6.7ChemAxon
pKa (Strongest Basic)9.96ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area51.16 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity97.4 m³·mol⁻¹ChemAxon
Polarizability37.62 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01ta-0069000000-0df9e0062a61b6f5b8992017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-006t-1019000000-aa0786df5ba267f0e0e92017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00lj-1390000000-8648b87e5be5af57865d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-03di-0049000000-c3cd0bedd322f4365f672017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0002-0009000000-510a4d7e28e894bf64232017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00lj-1390000000-8648b87e5be5af57865d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-02a2-0090000000-9feb05710c9986e21d462021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-054o-0980000000-898dbdc8c7ff49f386aa2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-05rc-0890000000-dc45a916bad1f29e719f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-0006-0095000000-d95a1ec4e22d84ab1cf02021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-02a2-0090000000-73e62abe4ba1240a31002021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0006-0095000000-5cb39aed9d0bb14ea38a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-0006-0095000000-a54974a771bb1b5fa4962021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-02cb-0090000000-9294686f4de04327da732021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-0006-0009000000-eb25fa2e3ca97a7ed87c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-aac18fa03a624667c9112021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-0006-0095000000-05e7cd025af07876a30f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-02a2-0090000000-e7c46dbf270136f4ea542021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-02a2-0090000000-455cfb312ea07df267fa2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0006-0096000000-f20f0a18703f41e3ac4a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-277b0f796e2f23a69cfc2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-26af6c94b94e28d921062016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01ox-0049000000-8a99a90c6557e0c04fd12016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0032-1091000000-2fa2513ead3fd70279122016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-d9089b3923b998a0fa982016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0019000000-5821cc312129ea3c5a1c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-0092000000-aab05b42a0932b71e3292016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityIsocorydine induces G2/M phase arrest by increasing cyclin B1 and p-CDK1 expression levels, which was caused by decreasing the expression and inhibiting the activation of Cdc25C. The phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment. Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the percentage of CD133+ PLC/PRF/5 cells. Interestingly, isocorydine treatment dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. (1)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/Sources(S)-Isocorydine is found in cherimoya.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB30184
PubChem Compound ID10143
ChEMBL IDCHEMBL489525
ChemSpider ID9737
KEGG IDC09549
UniProt IDNot Available
OMIM ID
ChEBI ID561752
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D4027.pdf
General References
  1. Sun H, Hou H, Lu P, Zhang L, Zhao F, Ge C, Wang T, Yao M, Li J: Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/m cell cycle arrest and apoptosis. PLoS One. 2012;7(5):e36808. doi: 10.1371/journal.pone.0036808. Epub 2012 May 18. [22623962 ]
  2. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Metal ion binding
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).
Gene Name:
CDK2
Uniprot ID:
P24941
Molecular Weight:
33929.215 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50250273
References
  1. Hegde VR, Borges S, Pu H, Patel M, Gullo VP, Wu B, Kirschmeier P, Williams MJ, Madison V, Fischmann T, Chan TM: Semi-synthetic aristolactams--inhibitors of CDK2 enzyme. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1384-7. doi: 10.1016/j.bmcl.2010.01.007. Epub 2010 Jan 7. [20097066 ]