Dicentrine
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Basic Info
| Common Name | Dicentrine(F05230) |
| 2D Structure | |
| Description | Dicentrine is an anticancer compound isolated from Lindera, a species of flowering plants. |
| FRCD ID | F05230 |
| CAS Number | 517-66-8 |
| PubChem CID | 101300 |
| Formula | C20H21NO4 |
| IUPAC Name | None |
| InChI Key | YJWBWQWUHVXPNC-AWEZNQCLSA-N |
| InChI | InChI=1S/C20H21NO4/c1-21-5-4-11-7-17-20(25-10-24-17)19-13-9-16(23-3)15(22-2)8-12(13)6-14(21)18(11)19/h7-9,14H,4-6,10H2,1-3H3/t14-/m0/s1 |
| Canonical SMILES | CN1CCC2=CC3=C(C4=C2C1CC5=CC(=C(C=C54)OC)OC)OCO3 |
| Isomeric SMILES | CN1CCC2=CC3=C(C4=C2[C@@H]1CC5=CC(=C(C=C54)OC)OC)OCO3 |
| Synonyms |
Dicentrine
Eximine
d-Dicentrine
517-66-8
O,N-Dimethyllitseferine
L-DICENTRINE
UNII-J2ZGT5M0N7
Dicentrine-(+)
CCRIS 3806
NSC 406035
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Aporphines |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Aporphines |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Aporphine - Benzoquinoline - Phenanthrene - Naphthalene - Quinoline - Tetrahydroisoquinoline - Benzodioxole - Anisole - Aralkylamine - Alkyl aryl ether - Benzenoid - Tertiary aliphatic amine - Tertiary amine - Organoheterocyclic compound - Azacycle - Oxacycle - Acetal - Ether - Hydrocarbon derivative - Organic oxygen compound - Organopnictogen compound - Organic nitrogen compound - Organonitrogen compound - Amine - Organooxygen compound - Aromatic heteropolycyclic compound |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 339.391 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Complexity | 502 |
| Monoisotopic Mass | 339.147 |
| Exact Mass | 339.147 |
| XLogP | 3.2 |
| Formal Charge | 0 |
| Heavy Atom Count | 25 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9887 |
| Human Intestinal Absorption | HIA+ | 0.9810 |
| Caco-2 Permeability | Caco2+ | 0.8527 |
| P-glycoprotein Substrate | Substrate | 0.7339 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8097 |
| Non-inhibitor | 0.8029 | |
| Renal Organic Cation Transporter | Inhibitor | 0.6170 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5163 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8753 |
| CYP450 2D6 Substrate | Substrate | 0.6229 |
| CYP450 3A4 Substrate | Substrate | 0.7457 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7119 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8237 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.7688 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.7057 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.6228 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5422 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.6910 |
| Non-inhibitor | 0.7998 | |
| AMES Toxicity | AMES toxic | 0.9106 |
| Carcinogens | Non-carcinogens | 0.9481 |
| Fish Toxicity | High FHMT | 0.9266 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8752 |
| Honey Bee Toxicity | Low HBT | 0.5475 |
| Biodegradation | Not ready biodegradable | 0.7804 |
| Acute Oral Toxicity | III | 0.7399 |
| Carcinogenicity (Three-class) | Non-required | 0.5880 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.3528 | LogS |
| Caco-2 Permeability | 1.5660 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.7139 | LD50, mol/kg |
| Fish Toxicity | 0.9455 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.6166 | pIGC50, ug/L |
Targets
- Uniprot ID:
- P35348; P35368; P25100
References
- Teng CM, Yu SM, Ko FN, Chen CC, Huang YL, Huang TF: Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla. Br J Pharmacol. 1991 Nov;104(3):651-6. [1686739 ]
- 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
References
- 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 ]