| Stereochemistry | ABSOLUTE |
| Molecular Formula | C18H25NO6 |
| Molecular Weight | 351.3942 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C\C=C1\C[C@@H](C)[C@](O)(CO)C(=O)OCC2=CCN3CC[C@@H](OC1=O)[C@@H]23
InChI
InChIKey=BCJMNZRQJAVDLD-CQRYIUNCSA-N
InChI=1S/C18H25NO6/c1-3-12-8-11(2)18(23,10-20)17(22)24-9-13-4-6-19-7-5-14(15(13)19)25-16(12)21/h3-4,11,14-15,20,23H,5-10H2,1-2H3/b12-3-/t11-,14-,15-,18-/m1/s1
Retrorsine (RTS) is a naturally occurring pyrrolizidine alkaloid (PA), isolated from Senecio retrorsus of South African origin. Retrorsine is a hepatotoxic Pyrrolizidine alkaloid which specifically inhibits the proliferation of hepatocytes and subsequently induces liver injury. The toxic effect of PAs has received plentiful clinical attention, yet the understanding of the mechanism of Retrorsine-induced hepatotoxicity is still limited. It has been reported that the CYPs mediated bioactivation is necessary for the toxicity of PAs and that CYP3A4 is the major isoform involved in the metabolism of Retrorsine. Together withCYP3A4, Organic cation transporter 1 mediates the liver-specific uptake of Retrorsine and plays an important role in RTS-induced hepatotoxicity. Retrorsine impairs liver regeneration after partial hepatectomy, not only by an S or G2/M phase block but also by a block located before the G1/S transition of the cell cycle. Treatment of rats with retrorsine, a pyrrolizidine alkaloid, results in a series of chronic and progressive hepatic lesions, including a long-lasting block in the cell cycle.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 2.25 µM [IC50] | |||
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
PubMed
Patents
Sample Use Guides
After 1 week of acclimatization, rats were randomized to receive two intraperitoneal injections, separated by a 2-week interval, of either retrorsine (Sigma–Aldrich, Bornem, Belgium) (30 mg/kg) or saline.
Route of Administration:
Intraperitoneal
Cultures of A204 human rhabdomyosarcoma cells were maintained in cell culture incubators. On day 1 (24 h later) an upper layer of 1 ml growth medium with and without the compound (Retrorsine) under investigation was added to the dishes. After 24 h, the upper layer of the medium was removed by aspiration, agarose culture surfaces washed once with 0.5 ml prewarmed growth medium, and then overlaid with 1 ml of fresh growth medium. Colony formation was examined at daily intervals by conventional light microscopy. Cell lines form a sufficient number of detectable colonies for analysis following 7 to 9 days incubation. Viable colonies were stained using a metabolizable tetrazolium salt, and colonies were counted using a Bausch & Lomb FAS-I1 image analysis system. Cultures were conducted in quadruplicate. Control cultures without drug were run at the same time.
SUBSTANCE RECORD
