IXABEPILONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H42N2O5S
Molecular Weight	506.698
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@]12C[C@H](NC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@]1(C)O2)C(\C)=C\C3=CSC(C)=N3

InChI

InChIKey=FABUFPQFXZVHFB-PVYNADRNSA-N

InChI=1S/C27H42N2O5S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)29-23(31)13-21(30)26(5,6)25(33)17(3)24(15)32/h11,14-15,17,20-22,24,30,32H,8-10,12-13H2,1-7H3,(H,29,31)/b16-11+/t15-,17+,20-,21-,22-,24-,27+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C27H42N2O5S
Molecular Weight	506.698
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description

Ixabepilone is an antineoplastic agent, epothilone and mitotic inhibitor that is FDA approved for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone binds directly to beta-tubulin subunits on microtubules, leading to suppression of microtubule dynamics. Ixabepilone suppresses the dynamic instability of alpha-beta-II and alpha-beta-III microtubules. The most common adverse reactions (≥20%) are peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. Inhibitors of CYP3A4 may increase plasma concentrations of ixabepilone.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin beta chain 8	Inhibitor 8,297		10.6 µM [EC50]
Cytochrome P450 3A4 127	Substrate 661		7.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434	Primary		Approved 8,429	IXEMPRA KIT

C_max

Value	Dose	Co-administered	Analyte	Population
252 ng/mL	40 mg/m² single, intravenous		IXABEPILONE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
2143 ng × h/mL	40 mg/m² single, intravenous		IXABEPILONE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
52 h	40 mg/m² single, intravenous		IXABEPILONE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
28%	40 mg/m² single, intravenous		IXABEPILONE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)	Disc. AE: Neuropathic pain... Other AEs: Anorexia, Stomatitis...
10 mg/m2 1 times / day multiple, intravenous	unhealthy, 10 years (range: 2 - 18 years)	DLT: Neutropenia, Fatigue...
6 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 18-80 years	Other AEs: Fatigue, Anorexia...
8 mg/m2 1 times / day multiple, intravenous	unhealthy, 18-80 years	DLT: Neutropenia...
6.8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 54 years (range: 22–75 years)	DLT: Low platelets, Arthralgia...

Showing 1 to 5 of 10 entries

Previous1 2Next

AEs

Show entries

AE	Significance	Dose	Population
Bilirubin increased	grade 2, 1 patient	8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)
Alopecia	grade 2, 2 patients	8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)
Anorexia	grade 3, 1 patient	8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)
Dehydration	grade 3, 1 patient	8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)
Dizziness	grade 3, 1 patient	8 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, 10 years (range: 2 - 18 years)

Showing 1 to 5 of 29 entries

Previous1 2 3 4 5 6Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1,737	inducer 389 inhibitor 1,767 substrate 1,037	inhibitor 1,852 substrate 1,217	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2A6 707 CYP2B6 810 CYP2C19 1,478 CYP2C8 911 CYP2E1 882 CYP3A4/5 278 P-gp 1,461	BCRP 561 CYP1A2 1,054 CYP2B6 664 CYP2C19 991 CYP2C8 693 CYP2E1 667 CYP3A4/5 85 CYP3A5 395 P-gp 1,537	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Show entries

Target	Modality	Activity	Clinical evidence
P-gp 1,650	inhibitor 3,277	inconclusive
CYP1A2 1,692	inhibitor 3,277	no [IC50 >30 uM]	unlikely
CYP2A6 739	inhibitor 3,277	no [IC50 >30 uM]	unlikely
CYP2B6 1,001	inhibitor 3,277	no [IC50 >30 uM]	unlikely
CYP2C19 1,553	inhibitor 3,277	no [IC50 >30 uM]	unlikely

Showing 1 to 5 of 14 entries

Previous1 2 3Next

Drug as victim

Show entries

Target	Modality	Activity	Clinical evidence
P-gp 1,537	substrate 3,367	inconclusive
CYP3A4 1,737	substrate 3,367	major	yes (co-administration study)
BCRP 561	substrate 3,367	no
CYP1A2 1,054	substrate 3,367	no
CYP2B6 664	substrate 3,367	no

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63605	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63605
ChemicalBook	CB61011739	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61011739
MolPort	MolPort-027-720-838	https://www.molport.com/shop/molecule-link/MolPort-027-720-838
ZINC	ZINC000003993846	http://zinc15.docking.org/substances/ZINC000003993846

Showing 1 to 4 of 4 entries

Previous1Next

PubMed

Title	Date	PubMed
[Efficacy and safety of ixabepilone (BMS-247550), a novel epothilone B analogue].	2008 Feb	18304905

Patents

Sample Use Guides

In Vivo Use Guide

40 mg/m2 infused over 3 hours every 3 weeks

Route of Administration: Intravenous

In Vitro Use Guide

Hepatocellular carcinoma cell lines were sensitive to ixabepilone, with the IC50 range 2.5–44.1 nmol/l.

Substance Class	Chemical
Record UNII	K27005NP0A
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

IXABEPILONE

Official Name

English

IXABEPILONE [MART.]

Common Name

English

IXABEPILONE [MI]

Common Name

English

1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMETHYL-3-((1E)-1-METHYL-2-(2-METHYLTHIAZOL-4-YL)ETHENYL)-17-OXA-4-AZABICYCLO(14.1.0)HEPTADECANE-5,9-DIONE

Common Name

English

ixabepilone [INN]

Common Name

English

Showing 1 to 5 of 22 entries

Previous1 2 3 4 5Next

Show entries

Classification Tree

Code System

Code

Breast Cancer

LIVERTOX

NBK547985

Taxane-Pocket Binding Agent

NCI_THESAURUS

C2584

Cellular Structure Alteration

NDF-RT

N0000175085

Other cytotoxic antibiotics

WHO-VATC

QL01DC04

Established Pharmacologic Class

NDF-RT

N0000175592

Showing 1 to 5 of 6 entries

Previous1 2Next

Show entries

Code System

Code

Type

Description

NSC

747973

PRIMARY

RXCUI

337523

PRIMARY

RxNorm

DRUG BANK

DB04845

PRIMARY

DAILYMED

K27005NP0A

PRIMARY

EVMPD

SUB33513

PRIMARY

Showing 1 to 5 of 22 entries

Previous1 2 3 4 5Next

Show entries

Related Record

Type

Details


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Amount:


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Comments:

The percentages ixabepilone bound to proteins at concentrations of 50, 500 and 5000 ng/mL were 76.6%, 72.0% and 67.1%, respectively. The protein binding of ixabepilone was not concentration dependent from 50 ng/mL to 5000 ng/mL.

Interaction Type:

BINDING

Amount:

[67.1 to 76.6] % (average)