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Details

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
Structure of RETRORSINE

SMILES

[H][C@@]12[C@H]3CCN1CC=C2COC(=O)[C@@](O)(CO)[C@H](C)C\C(=C\C)C(=O)O3

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

HIDE SMILES / InChI

Molecular Formula C18H25NO6
Molecular Weight 351.3942
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11493272 | https://www.ncbi.nlm.nih.gov/pubmed/3210016 | https://www.ncbi.nlm.nih.gov/pubmed/28095673 | https://www.ncbi.nlm.nih.gov/pubmed/24799337

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.25 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
PubMed

PubMed

TitleDatePubMed
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.
1991 Jan-Feb
Patents

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
In Vitro Use Guide
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 Class Chemical
Created
by admin
on Fri Dec 15 19:45:34 GMT 2023
Edited
by admin
on Fri Dec 15 19:45:34 GMT 2023
Record UNII
XJ86XWL8IY
Record Status Validated (UNII)
Record Version
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Name Type Language
RETRORSINE
HSDB   MI  
Common Name English
RETRORSINE [IARC]
Common Name English
RETRORSINE [HSDB]
Common Name English
12,18-DIHYDROXYSENECIONAN-11,16-DIONE
Common Name English
RETRORSINE [MI]
Common Name English
NSC-107659
Code English
Code System Code Type Description
FDA UNII
XJ86XWL8IY
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
PRIMARY
CAS
480-54-6
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
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MERCK INDEX
m9560
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID6021242
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
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HSDB
3530
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
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NSC
107659
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
PRIMARY
PUBCHEM
5281743
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
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MESH
C003300
Created by admin on Fri Dec 15 19:45:34 GMT 2023 , Edited by admin on Fri Dec 15 19:45:34 GMT 2023
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