| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H41NO5S |
| Molecular Weight | 491.683 |
| Optical Activity | ( - ) |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H]1CCCC(C)=CC[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@H]1O)C(\C)=C\C2=CSC(C)=N2
InChI
InChIKey=XOZIUKBZLSUILX-GIQCAXHBSA-N
InChI=1S/C27H41NO5S/c1-16-9-8-10-17(2)25(31)19(4)26(32)27(6,7)23(29)14-24(30)33-22(12-11-16)18(3)13-21-15-34-20(5)28-21/h11,13,15,17,19,22-23,25,29,31H,8-10,12,14H2,1-7H3/b16-11-,18-13+/t17-,19+,22-,23-,25-/m0/s1
| Molecular Formula | C27H41NO5S |
| Molecular Weight | 491.683 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
Epothilone D (KOS-862 or BMS-241027) is an intermediary obtained in the synthesis of members of the epothilone family and is a small-molecule microtubule stabilizer. It was investigated in Phase II trials in colorectal, metastatic breast and non-small-cell lung cancers. However, development was discontinued in 2007 in favor of a second-generation analog with a better safety profile. This drug also was studied for the treatment of Alzheimer's disease. The study ended in October 2013, and evaluation of epothilone D for Alzheimer's disease was subsequently discontinued. The mechanism by which epothilones induce microtubule polymerization appears to be similar to that of paclitaxel, in that epothilones compete with paclitaxel for binding to microtubules and suppress microtubule dynamics in a manner similar to that of paclitaxel.
CNS Activity
Originator
Approval Year
Cmax
AUC
Doses
AEs
Sourcing
PubMed
Sample Use Guides
Alzheimer's Disease: BMS-241027 (Epothilone D) in 40 patients with mild Alzheimer's disease whose MMSE at screening was between 20 and 26. The trial compares 0.003, 0.01, and 0.03 mg/kg infused once a week for nine weeks to placebo.
Route of Administration:
Intravenous
The effects of 1, 10 and 100 nM concentrations of epothilone (EPO) D in four malignant human glioma cell lines were measured using a microtiter-tetrazolium assay. In all four human glioma cell lines, 10 and 100 nM concentrations of the drug, applied for 96 h, leading to a highly significant decrease in the viable cell number (p < 0.001). A mean reduction of the viable cell number between 30% and 40% (60% and 90%) was observed for a drug concentration of 10 nM (100 nM). A round cell morphology occurred in most EPO treated cells and the organized network of microtubules was shrunk in these round cells. These results prove that EPOs have antiproliferative effects in glioma cells and affect their tubulin cytoskeleton, as it was previously observed in several types of carcinoma cells.
