EPOTHILONE D

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H41NO5S
Molecular Weight	491.683
Optical Activity	( - )
Defined Stereocenters	5 / 5
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

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

HIDE SMILES / InChI

Molecular Formula	C27H41NO5S
Molecular Weight	491.683
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: http://www.alzforum.org/therapeutics/epothilone-d | https://www.ncbi.nlm.nih.gov/pubmed/15242255 | https://www.ncbi.nlm.nih.gov/pubmed/15143095

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

Targets

Primary Target	Pharmacology	Condition	Potency
microtubules 1 Target ID: microtubules Sources: https://www.ncbi.nlm.nih.gov/pubmed/15143095	Binding Agent 1064

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: http://www.alzforum.org/therapeutics/epothilone-d	Primary	Phase I 428	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15242255	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15242255	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15242255	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
2737.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4037 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22072399	100 mg/m² 1 times / week multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3001.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D HYDROLYTIC METABOLITE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
9451.7 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12093 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22072399	100 mg/m² 1 times / week multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16928.2 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D HYDROLYTIC METABOLITE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22072399	100 mg/m² 1 times / week multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EPOTHILONE D plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19775943	125 mg/m² single, intravenous dose: 125 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	EPOTHILONE D HYDROLYTIC METABOLITE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	DLT: Visual Hallucination, Dehydration... Other AEs: Syncope... Dose limiting toxicities: Visual Hallucination (1 pt) Dehydration (1 pt) Diarrhea (severe, 1 pt) Nausea (severe, 1 pt) Vomiting (severe, 1 pt) Other AEs: Syncope (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
100 mg/m2 2 times / 3 weeks multiple, intravenous (total daily dose) Studied dose Dose: 100 mg/m2, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 2 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 10 Health Status: unhealthy Condition: solid tumours Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	DLT: visual hallucination, Peripheral sensory neuropathy... Dose limiting toxicities: visual hallucination (grade 2, 2 patients) Peripheral sensory neuropathy (grade 2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
100 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Studied dose Dose: 100 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 10 Health Status: unhealthy Condition: tumor cancer Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	DLT: Peripheral sensory neuropathy... Dose limiting toxicities: Peripheral sensory neuropathy (grade 2, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/22072399

AEs

AE	Significance	Dose	Population
Syncope	1 pt	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Visual Hallucination	1 pt DLT	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Dehydration	1 pt DLT, Disc. AE	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Diarrhea	severe, 1 pt DLT	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Nausea	severe, 1 pt DLT	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Vomiting	severe, 1 pt DLT	120 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Highest studied dose Dose: 120 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 2 Health Status: unhealthy Condition: solid tumors Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Peripheral sensory neuropathy	grade 2, 2 patients DLT	100 mg/m2 2 times / 3 weeks multiple, intravenous (total daily dose) Studied dose Dose: 100 mg/m2, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 2 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 10 Health Status: unhealthy Condition: solid tumours Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
visual hallucination	grade 2, 2 patients DLT	100 mg/m2 2 times / 3 weeks multiple, intravenous (total daily dose) Studied dose Dose: 100 mg/m2, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 2 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 10 Health Status: unhealthy Condition: solid tumours Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399
Peripheral sensory neuropathy	grade 2, 1 pt DLT	100 mg/m2 3 times / 3 weeks multiple, intravenous (total daily dose) Studied dose Dose: 100 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 3 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/22072399	unhealthy n = 10 Health Status: unhealthy Condition: tumor cancer Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22072399

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY445209	https://www.001chemical.com/chem/search?q=DY445209
ApexBio Technology	A3394	https://www.apexbt.com/catalogsearch/result/?q=A3394
AstaTech	40768	http://astatechinc.com/CPSResult.php?CRNO=40768
Chem Scene	CS-0655	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0655
Excenen	EX-A495	http://www.excenen.com/searchresultlist.php?id=EX-A495
MedChem Express	HY-15278	https://www.medchemexpress.com/search.html?q=HY-15278&ft=&fa=&fp=
MolPort	MolPort-028-744-727	https://www.molport.com/shop/molecule-link/MolPort-028-744-727
Toronto Research Chemicals	E589000	https://www.trc-canada.com/product-detail/?CatNum=E589000
eMolecules	60180276	https://orderbb.emolecules.com/search/#?query=60180276
mcule	MCULE-4342762356	https://mcule.com/MCULE-4342762356/

PubMed

Title	Date	PubMed
Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action.	1995 Jun 1	7757983
Epothilone D (Kosan/Roche).	2004 Jun	15242255
Epothilones: mechanism of action and biologic activity.	2004 May 15	15143095
Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy.	2010 Oct 13	20943926
Epothilone D and its 9-Methyl analogues: combinatorial syntheses, conformation, and biological activities.	2013 Oct	23994325

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:29:43 GMT 2023` Edited by `admin` on `Fri Dec 15 15:29:43 GMT 2023`
Record UNII	T0358E0YUF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EPOTHILONE D

Common Name

English

OXACYCLOHEXADEC-13-ENE-2,6-DIONE, 4,8-DIHYDROXY-5,5,7,9,13-PENTAMETHYL-16-((1E)-1-METHYL-2-(2-METHYL-4-THIAZOLYL)ETHENYL)-, (4S,7R,8S,9S,13Z,16S)-

Systematic Name

English

12,13-DESOXYEPOTHILONE B, CIS

Common Name

English

(-)-DESOXYEPOTHILONE B

Common Name

English

EPOTHILONE D [MI]

Common Name

English

12,13-DESOXYEPOTHILONE B

Common Name

English

KOS-862

Code

English

NSC-703147

Code

English

R1492

Code

English

DESOXYEPOTHILONE B

Common Name

English

Epothilone D [WHO-DD]

Common Name

English

R-1492

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1922