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Epothilone D (formerly known as KOS 862; KOS-862; desoxyepothilone B) is a potent microtubule stabilizing agent that has high anticancer activity. It is a naturally occurring polyketide that was separated from Sorangium cellulosum, a myxobacterium. When epothilone D binds to tubulin, it prevents microtubule disintegration, which in turn stops mitosis, cellular growth, and motility.
Physicochemical Properties
| Molecular Formula | C27H41NO5S |
| Molecular Weight | 491.6831 |
| Exact Mass | 491.27 |
| Elemental Analysis | C, 65.95; H, 8.40; N, 2.85; O, 16.27; S, 6.52 |
| CAS # | 189453-10-9 |
| Related CAS # | (16R)-Epothilone D |
| PubChem CID | 447865 |
| Appearance | White to light yellow solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 657.7±55.0 °C at 760 mmHg |
| Melting Point | 63-66°C |
| Flash Point | 351.6±31.5 °C |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.526 |
| LogP | 3.69 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 34 |
| Complexity | 777 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | S1C(C([H])([H])[H])=NC(=C1[H])/C(/[H])=C(\C([H])([H])[H])/[C@]1([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])[H])[C@@]([H])([C@@]([H])(C([H])([H])[H])C(C(C([H])([H])[H])(C([H])([H])[H])[C@]([H])(C([H])([H])C(=O)O1)O[H])=O)O[H] |t:24| |
| InChi Key | XOZIUKBZLSUILX-GIQCAXHBSA-N |
| InChi Code | 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 |
| Chemical Name | (4S,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione |
| Synonyms | KOS 862; (-)-Desoxyepothilone B; (-)-Epothilone D; KOS-862; 12,13-Deoxyepothilone B; KOS862; 12,13-Desoxyepothilone B; Desoxyepothilone B; Epo D; Epothilone D; NSC 703147. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Microtubule/Tubulin | |
| ln Vitro |
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| ln Vivo |
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| Animal Protocol | Mice: Three groups of mice (n = 3) are given intraperitoneal (i.p.) injections of 3.7 mg/kg of dissolved Epothilone D (epoD) in 100% DMSO. The mice are then put to sleep using approved methods at intervals of 0.25 to 24 hours. In a different study, three groups of mice (n=3) are injected with 3 mg/kg of epoD in 100% DMSO, and four, six, and ten days later, they are put to death. Using LC-MS/MS procedures, the levels of epothilone D (epoD) in brain and blood samples are ascertained. For a duration of three months, groups (n=10–13) of three-month-old PS19 tau Tg mice or their three-month-old non-Tg littermates receive weekly intraperitoneal injections (i.p.) of vehicle (DMSO), 1 mg/kg epoD, or 3 mg/kg epothilone D (ep. Pets are weighed every week and watched for indications of unusual behavior or distress. Testing of the mice's motor and cognitive abilities occurs after the last dosage. Upon euthanasia, the optic nerve (ON) and brain are removed for immunohistochemical examination. An organ weight assessment and necropsy are also performed on a subset of mice from each group. | |
| References |
[1]. Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma. Invest New Drugs. 2012 Dec;30(6):2294-302. [2]. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. |
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| Additional Infomation |
Epothilone D is an epithilone that is epithilone C in which the hydrogen at position 13 of the oxacyclohexadec-13-ene-2,6-dione macrocycle has been replaced by a methyl group. It has a role as a microtubule-stabilising agent. Epothilone D has been reported in Myxococcus xanthus, Sorangium cellulosum, and Streptomyces venezuelae with data available. Epothilone D is a natural polyketide compound isolated from the myxobacterium Sorangium cellulosum. Also known as desoxyepothilone B, epothilone D binds to tubulin and inhibits the disassembly of microtubules, resulting in the inhibition of mitosis, cellular proliferation, and cell motility. (NCI04) Drug Indication Investigated for use/treatment in colorectal cancer, lung cancer, breast cancer, solid tumors, and prostate cancer. Mechanism of Action The principal mechanism of the epothilone class is inhibition of microtubule function. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 100 mg/mL (~203.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0338 mL | 10.1692 mL | 20.3384 mL | |
| 5 mM | 0.4068 mL | 2.0338 mL | 4.0677 mL | |
| 10 mM | 0.2034 mL | 1.0169 mL | 2.0338 mL |