Absorption, Distribution and Excretion
Animal studies have shown that the highest concentrations are found in the liver, lungs, kidneys, and spleen. Following injection, the radioactive material is rapidly excreted in urine and feces within 16 hours (84% or more). More than 1.5% of the dose remains in the liver after 16 hours. A small amount (0.04%) of the dose is transferred to milk within 16 hours; most of the radioactive material is present in skim milk, indicating that the pyrrolizidine alkaloids are transferred to milk as water-soluble metabolites. …The binding to calf thymus DNA and microsomal macromolecules was determined in vitro. Binding was weakened in the absence of oxygen or NADPH-generating systems, or by boiling the microsomes. No inhibitory effect of potassium cyanide on binding was observed. Pyrrolizidine alkaloids…To investigate its transfer to milk, a cow was orally administered a single dose of 1 mg/kg body weight of (3H) senna. The presence of radioactive substances from this compound in blood and milk was subsequently monitored. Based on senglitin, the blood concentration exceeded 100 ng/mL within the first 18 hours after administration. At 54 hours, the blood concentration remained at 11 ng/mL. Similar alkaloid levels were observed in milk. At 64 hours, the milk concentration was still 5 ng/mL. A total of 0.16% of the dose was excreted through milk. Three weeks after administration, 40 ng/g of alkaloids (0.06% of the administered dose) were detected in the liver. In addition to unchanged senglitin and retroline, N-oxides were also detected in milk casserotonin metabolites (11.2% at 27 hours). Metabolites/Metabolites Typically, hepatotoxic pyrrolizidine alkaloids are metabolized in the rat liver to form hydrolysates, N-oxides, and dehydropyrrolizidine (pyrrole) derivatives. ...Dehydroalkaloids are highly reactive alkylating agents... /Pyrrolizidine alkaloids/
Dehydroretronine...water-soluble pyrrole metabolites of senna...have been shown to be carcinogenic. /Pyrrolizidine alkaloids/
In animals, the main metabolic pathways of pyrrolizidine alkaloids are: (a) ester hydrolysis; (b) N-oxidation; (c) nuclear dehydrogenation of pyrrolizidine to form pyrrole derivatives. Pathways (a) and (b) are considered detoxification mechanisms. Pathway (c) produces toxic metabolites. Pathway (a) occurs in the liver and blood; pathways (b) and (c) are mediated by the hepatic microsomal mixed-function oxidase system. /Pyrrolizidine alkaloids/

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Biological half-life
Only a relatively small proportion of the administered dose remains in the body within a few hours. The majority of this remains as metabolites bound to tissue components. Following intravenous injection in animals, pyrrolizidine N-oxide disappears from the serum, with an initial half-life of 3-20 minutes. /Pyrrolizidine alkaloids/

Non-Human Toxicity Values
Mouse intravenous LD50: 90 mg/kg Rat intravenous LD50: 80 mg/kg Male rat intraperitoneal LD50: 77 mg/kg (95% confidence interval: 71-86 mg/kg) Female rat intraperitoneal LD50: 83 mg/kg (95% confidence interval: 77-90 mg/kg)

[1]. Cytotoxicity of Senecio in macrophages is mediated via its induction of oxidative stress. Res Vet Sci. 2009 Aug;87(1):85-90.

[2]. Effect of seneciphylline and senecionine on hepatic drug metabolizing enzymes in rats. J Ethnopharmacol. 1984 Dec;12(3):271-8.

Senecio alkaloid is a white powder. (NTP, 1992)
LSM-2853 is a citrate compound.
Sensio alkaloid has been reported to exist in Senecio carniolica, Senecio rodriguezii, and other organisms with relevant data.
Mechanism of Action

Mixed-function oxidases activate the alkaloid to produce pyrrole dehydroalkaloids, which are active alkylating agents. Metabolites bind to hepatocytes, leading to liver necrosis. Some metabolites are released into the bloodstream and are believed to reach the lungs via the liver, causing vascular damage. Pyrrole metabolites are cytotoxic, acting on hepatocytes and vascular endothelial cells in the liver and lungs. Pyrrolizidine Alkaloids
This study investigated the effects of oral administration of the pyrrolizidine alkaloid, Senecio scandens (from the plant Senecio scandens), on the activities of epoxide hydrolase, glutathione S-transferase, aminopyrine N-demethylase, and aryl hydrocarbon hydroxylase (AHH) in the liver microsomes of young male albino rats. The results showed that Senecio scandens significantly increased the activities of epoxide hydrolase and glutathione S-transferase, but decreased the activities of cytochrome P-450 and its associated monooxygenases. …Senecio scandens…had no significant in vitro effects on the studied hepatic drug-metabolizing enzymes; both alkaloids slightly stimulated the activity of epoxide hydrolase, while Senecio scandens slightly decreased the activity of aminopyrine demethylase.

C18H23NO5

333.3789

333.157

480-81-9

5281750

White to off-white solid

1.3±0.1 g/cm3

577.7±50.0 °C at 760 mmHg

217ºC

303.2±30.1 °C

0.0±3.6 mmHg at 25°C

1.581

0.81

1

6

0

24

650

3

O1C(/C(=C(/[H])\C([H])([H])[H])/C([H])([H])C(=C([H])[H])[C@](C([H])([H])[H])(C(=O)OC([H])([H])C2=C([H])C([H])([H])N3C([H])([H])C([H])([H])[C@]1([H])[C@]32[H])O[H])=O

FCEVNJIUIMLVML-QPSVUOIXSA-N

InChI=1S/C18H23NO5/c1-4-12-9-11(2)18(3,22)17(21)23-10-13-5-7-19-8-6-14(15(13)19)24-16(12)20/h4-5,14-15,22H,2,6-10H2,1,3H3/b12-4-/t14-,15-,18-/m1/s1

(1R,4Z,7R,17R)-4-ethylidene-7-hydroxy-7-methyl-6-methylidene-2,9-dioxa-14-azatricyclo[9.5.1.014,17]heptadec-11-ene-3,8-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~7.69 mg/mL (~23.07 mM)

Solubility in Formulation 1: ≥ 0.77 mg/mL (2.31 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 7.7 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.

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Solubility in Formulation 2: ≥ 0.77 mg/mL (2.31 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 7.7 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.

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Solubility in Formulation 3: ≥ 0.77 mg/mL (2.31 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 7.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)