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Veratramine (formerly known as NSC17821 and NSC23880) is a novel, potent and selective natural modulator of AP-1 which is useful as a signal transduction inhibitor for treating tumors. Veratramine is a hypotensive alkaloid isolated from the rhizomes of Veratrum. Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA. Veratramine selectively binds to a specific site (TRE 5'-TGACTCA-3') of the AP-1 target DNA sequence and regulates AP-1-dependent gene transcription without interfering with cystosolic signaling cascades that might lead to AP-1 activation.
Physicochemical Properties
| Molecular Formula | C27H39NO2 |
| Molecular Weight | 409.6041 |
| Exact Mass | 409.298 |
| CAS # | 60-70-8 |
| PubChem CID | 6070 |
| Appearance |
CRYSTALS NEEDLES |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 565.0±50.0 °C at 760 mmHg |
| Melting Point | 122-124ºC |
| Flash Point | 86.2±20.7 °C |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.601 |
| LogP | 4.9 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 30 |
| Complexity | 676 |
| Defined Atom Stereocenter Count | 8 |
| SMILES | O([H])[C@@]1([H])C([H])([H])C([H])([H])[C@@]2(C([H])([H])[H])C(=C([H])C([H])([H])[C@@]3([H])C4C([H])=C([H])C([C@]([H])(C([H])([H])[H])[C@@]5([H])[C@@]([H])(C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])N5[H])O[H])=C(C([H])([H])[H])C=4C([H])([H])[C@]23[H])C1([H])[H] |
| InChi Key | MALFODICFSIXPO-KFKQDBFTSA-N |
| InChi Code | InChI=1S/C27H39NO2/c1-15-11-25(30)26(28-14-15)17(3)20-7-8-21-22-6-5-18-12-19(29)9-10-27(18,4)24(22)13-23(21)16(20)2/h5,7-8,15,17,19,22,24-26,28-30H,6,9-14H2,1-4H3/t15-,17-,19-,22-,24-,25+,26-,27-/m0/s1 |
| Chemical Name | (3beta,23beta)-14,15,16,17-Tetradehydroveratraman-3,23-diol |
| Synonyms | NSC 17821; NSC17821; NSC-17821; NSC 23880; NSC-23880; NSC23880. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vivo | Total alkaloids (VTA) and veratramine of Veratrum nigrum L. were tested for hypotensive effect using spontaneously hypertensive rats (SHR). Acute toxicities were also evaluated. There was a dose-dependent reduction in blood pressure and heart rate after a single ingestion (1.0 to 4.0 mg/kg, intragastric administration) of VTA. A single oral ingestion (0.56 to 2.24 mg/kg) of veratramine, the major component of VTA, dose-dependently decreased blood pressure and heart rate, suggesting that veratramine was involved in the hypotensive effect of VTA in SHR. The hypotensive effects of VTA and veratramine are directly positively correlated with the dosage. Side effects were not obvious.[1] |
| Toxicity/Toxicokinetics |
Toxicity Summary Veratramine produces a characteristic excitatory action on the central nervous system, producing both tremor and a characteristic "struggling" behavior. This behavioral excitation is accompanied by changes in serotonin content in hypothalamus. The central serotonin agonist methysergide in doses of 5--15 mg per kg produces a dose-dependent inhibition of veratramine's action, while parachlorophenylalanine has no effect. (A15440) |
| References |
[1]. Hypotensive effect and toxicology of total alkaloids and veratramine from roots and rhizomes of Veratrum nigrum L. in spontaneously hypertensive rats. Pharmazie. 2008 Aug;63(8):606-10. [2]. Puqienine F, a novel veratramine alkaloid from the bulbs of Fritillaria puqiensis. Chem Pharm Bull (Tokyo). 2006 May;54(5):722-4. |
| Additional Infomation |
Veratramine is a piperidine alkaloid comprising the 14,15,16,17-tetradehydro derivative of veratraman having two hydroxy groups at the 3- and 23-positions. It derives from a hydride of a veratraman. Veratramine has been reported in Veratrum dahuricum, Veratrum grandiflorum, and other organisms with data available. Veratramine is a hypotensive alkaloid isolated from the rhizomes of Veratrum. Mechanism of Action THE EFFECTS OF VERATRAMINE ON TRANSMEMBRANE POTENTIALS OF THE ISOLATED RIGHT ATRIAL PREPN OF THE CAT WERE EXAMINED. VERATRAMINE SLOWED THE SPONTANEOUS RATE & PPTD A CHARACTERISTIC RHYTHM CONSISTING OF ALTERNATING PERIODS OF ASYSTOLE & NORMAL ATRIAL RHYTHM (PERIODIC RHYTHM). AFTER LARGE DOSES OR CONTINUED EXPOSURE TO LOW DOSES OF VERATRAMINE, ELECTRICAL & MECHANICAL ACTIVITY OF THE ATRIA CEASED; SUBSEQUENTLY ACTIVITY RESUMED ONLY IN A DISCRETE AREA WITHIN WHICH ACTION POTENTIALS WERE CONSISTENT WITH PACEMAKER CHARACTERISTICS. L-ETHOMOXANE HYDROCHLORIDE CAUSED 1/30TH & BETWEEN 1/10 & 1/20TH OF THE NEGATIVE CHRONOTROPIC EFFECT INDUCED BY VERATRAMINE ON THE DOG HEART-LUNG PREPN & ON THE ISOLATED GUINEA PIG ATRIUM, RESPECTIVELY. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 100 mg/mL (~244.14 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4414 mL | 12.2070 mL | 24.4141 mL | |
| 5 mM | 0.4883 mL | 2.4414 mL | 4.8828 mL | |
| 10 mM | 0.2441 mL | 1.2207 mL | 2.4414 mL |