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Sagopilone

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New Epothilone
Sagopilone
Names
IUPAC name (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,12,16-tetramethyl-3-(2-methyl-1,3-benzothiazol-5-yl)-10-prop-2-enyl-4,17-dioxabicycloheptadecane-5,9-dione
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.207.513 Edit this at Wikidata
EC Number
  • 682-320-6
KEGG
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C30H41NO6S/c1-7-9-20-27(34)17(2)10-8-13-30(6)25(37-30)15-22(19-11-12-23-21(14-19)31-18(3)38-23)36-26(33)16-24(32)29(4,5)28(20)35/h7,11-12,14,17,20,22,24-25,27,32,34H,1,8-10,13,15-16H2,2-6H3/t17-,20+,22-,24-,25-,27-,30+/m0/s1Key: BFZKMNSQCNVFGM-UCEYFQQTSA-N
SMILES
  • C1CCC2((O2)C(OC(=O)C(C(C(=O)(1O)CC=C)(C)C)O)C3=CC4=C(C=C3)SC(=N4)C)C
Properties
Chemical formula C30H41NO6S
Molar mass 543.72 g·mol
Hazards
GHS labelling:
Pictograms GHS06: ToxicGHS08: Health hazard
Signal word Danger
Hazard statements H300, H341, H361
Precautionary statements P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

Sagopilone is a fully synthetic macrolide of the epothilone family with the molecular formula C30H41NO6S. The mechanism of action is similar to taxanes, as they bind to the microtubule and prohibit cell division. These toxic properties and its possibility to cross the blood-brain barrier makes it a promising cancer medication.

Substance class

Sagopilone, also known as ZK-EPO belongs to the epothilones which are formed out of polyketides.

Structure

Sagopilone is a 16-bond macrolide structure, a macrocycle with inner ester structure. With its C30H41NO6S  formula and a molecular weight of only 543.7 g/mol sagopilone belongs to the low molecular weight epothilones

Sagopilone has similarities in structure and mechanism of actions with epothilone, especially epothilone B. The mechanism of action is similar to the taxanes. It binds to the microtubule of the cell and therefore prevents cell division. Which makes it acutely toxic.

Sagopilone contains 2 hydrogen bond donor and 8 acceptor, 3 rotatable bonds and 7 stereocenters.

Biological effects and usage

Epothilones are a novel class of natural microtubules-stabilizing products. They show potential activity in an expanded spectrum of tumor indications.

Microtubules are polymeric structures. They are composed of alpha- and beta-tubulin heterodimers. Sagopilone induces tubulin polymerization and therefore shows antitumor activity.

In the cell, sagopilone localizes predominantly to the cytoskeletal compartment. Sagopilone treated cells show mitotic abnormalities which lead to induction of cell cycle arrest at metaphase (in HCT116 cells). Induction of the apoptosis follows together with mitochondrial transmembrane potential dissipation (activation of caspase-3 and - 9, mitochondrial cytochrome c release).

Sagopilone was tested in phase II clinical trials and has been shown to be clinically active in platinum- resistant and -sensitive ovarian cancer, NSCLC, prostate cancer, glioblastoma and melanoma tumor cells.

References

  1. "Sagopilone". pubchem.ncbi.nlm.nih.gov.
  2. Clin Oncol 2007, 25, p. 3415-20
  3. Marupudi, Neena I; Han, James E; Li, Khan W; Renard, Violette M; Tyler, Betty M; Brem, Henry (September 2007). "Paclitaxel: a review of adverse toxicities and novel delivery strategies". Expert Opinion on Drug Safety. 6 (5): 609–621. doi:10.1517/14740338.6.5.609. PMID 17877447.
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