Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C13H15NO2 |
Molecular Weight | 217.2637 |
Optical Activity | ( - ) |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12CCCCN1[C@H]3C[C@@]24OC(=O)C=C4C=C3
InChI
InChIKey=SWZMSZQQJRKFBP-WZRBSPASSA-N
InChI=1S/C13H15NO2/c15-12-7-9-4-5-10-8-13(9,16-12)11-3-1-2-6-14(10)11/h4-5,7,10-11H,1-3,6,8H2/t10-,11-,13+/m1/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/25845059Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/28943934 | https://www.ncbi.nlm.nih.gov/pubmed/27792748 |
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845059
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/28943934 | https://www.ncbi.nlm.nih.gov/pubmed/27792748 |
Securinine is a plant-derived alkaloid from the Securinega plant that has been used clinically as a therapeutic for primarily neurological related diseases. Securinine is well-known GABAA antagonist and recently it was found that Securinine is able to up-regulate p53 protein and to modulate the related family member p73 protein in a p53-dependent fashion, inducing p73 in the HCT116 p53(-) cells and down-regulating it in the p53(+) cells. Securinine induces G1 phase cell cycle arrest, upregulates expression of p53 and Bax, and downregulates expression of Bcl-2, PI3K, mTOR, and p70s6k in breast cancer cells and promyelocytic leukemia cells. Securinine activates p38 MAPK, enhancing monocyte antibacterial activity in vitro as well. This compound also exhibits antimicrobial activity against Alternaria, Curvularia, and Helminthosporum. Additionally, securinine decreases AChE activity and suppresses amyloid-β (Aβ)-induced glial inflammatory responses in animal models of Alzheimer’s disease, improving cognitive deficits. Securinine’s activity as a GABA antagonist, likely explains its reported clinical success in limited studies for the treatment of neurological conditions such as amyotrophic lateral sclerosis (ALS), poliomyelitis and multiple sclerosis. Securinine has not been utilized in the United States, it has been used clinically in several other countries particularly China and Russia. In China, it is considered one of the 50 fundamental Chinese herbs and is used in Chinese herbal medicine.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2985189 |
57.0 µM [IC50] | ||
Target ID: CHEMBL2096978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27777067 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://chem.nlm.nih.gov/chemidplus/rn/5610-40-2
Curator's Comment: Zhonghua Yixue Zazhi. Chinese Medical Journal. Vol. 54, Pg. 234, 1974.
LD50: mouse/subcutaneous 20.42mg/kg; mouse/oral 270mg/kg; mouse/intravenous 6.23mg/kg; mouse/intraperitoneal 31.8mg/kg; mouse/intramuscular 19.32mg/kg
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28943934
The human lung cancer A549 cell line were used for activity evaluation. The exponentially growing human lung cancer cell suspension (5,000 cells/100 μl) was seeded into each well of 96 well plates. The cells were pre incubated for 24 h in the humidified incubator at 37˚C with 5% CO2. Various concentrations of L securinine from 0 to 160 μg/ml (10 μl) were added into each well. The cells were then incubated for 24, 36 and 48 h in the incubator. CCK 8 solution (10 μl; cat no. KGA317; Nanjing KeyGen Biotech Co., Ltd., Nanjing, China) was added to each well and incubated for 3 h. The absorbance of the wells at 450 nm was measured using a microplate reader
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NCI_THESAURUS |
C221
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m9829
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442872
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Securinine
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C000785
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C81359
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)