Sagopilone

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-dioxabicyclo[14.1.0]heptadecane-5,9-dione
Identifiers
CAS Number	305841-29-6
3D model (JSmol)	Interactive image
ChEBI	CHEBI:177512
ChEMBL	ChEMBL2304041
ChemSpider	9459163
DrugBank	DB12391
ECHA InfoCard	100.207.513
EC Number	682-320-6
KEGG	D09721
PubChem CID	11284169
UNII	KY72JU32FO
CompTox Dashboard (EPA)	DTXSID30952866
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/s1 Key: BFZKMNSQCNVFGM-UCEYFQQTSA-N
SMILES C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]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−1
Hazards
GHS labelling:
Pictograms
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 [77 °F], 100 kPa). Infobox references

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.