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Details

Stereochemistry ABSOLUTE
Molecular Formula C45H54F2N4O8.2C4H6O6
Molecular Weight 1117.1027
Optical Activity UNSPECIFIED
Defined Stereocenters 14 / 14
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VINFLUNINE DITARTRATE

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.[H][C@@]12N3CC[C@@]14C5=C(C=C(OC)C(=C5)[C@]6(C[C@@H]7C[C@H](C[N@@](C7)CC8=C6NC9=C8C=CC=C9)C(C)(F)F)C(=O)OC)N(C)[C@@]4([H])[C@](O)([C@H](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC

InChI

InChIKey=YIHUEPHBPPAAHH-IIQAEXPMSA-N
InChI=1S/C45H54F2N4O8.2C4H6O6/c1-8-42-14-11-16-51-17-15-43(36(42)51)30-19-31(34(56-5)20-33(30)49(4)37(43)45(55,40(54)58-7)38(42)59-25(2)52)44(39(53)57-6)21-26-18-27(41(3,46)47)23-50(22-26)24-29-28-12-9-10-13-32(28)48-35(29)44;2*5-1(3(7)8)2(6)4(9)10/h9-14,19-20,26-27,36-38,48,55H,8,15-18,21-24H2,1-7H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t26-,27+,36-,37+,38+,42+,43+,44-,45-;2*1-,2-/m011/s1

HIDE SMILES / InChI
Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula C45H54F2N4O8
Molecular Weight 816.9291
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18347163 | http://adisinsight.springer.com/drugs/800010899

Vinflunine (Javlor) is the first fluorinated microtubule inhibitor belonging to the Vinca alkaloids family. Vinflunine, at the lowest effective concentrations, interacts with the Vinca alkaloid binding site on tubulin, suppresses microtubule dynamics (switching at microtubule ends between phases of slow growth and rapid shortening) and microtubule treadmilling (growth at the plus end and shortening at the minus end of the microtubule), causes cell cycle arrest which appears on fluorescence-activated cell sorting analysis as a G2 + M phase arrest, and is associated with an accumulation of cells in mitosis leading to cell death via apoptosis. Vinflunine has been been approved for advanced or metastatic transitional cell carcinoma of the urothelial tract. Pierre Fabre submitted an extension to the EU authorisation to add treatment of advanced breast cancer.

Originator

Approval Year

Unknown
134361
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8228
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
Javlor

Approved Use

Javlor (vinflunine ditartrate) is indicated in monotherapy for the treatment of adult patients with advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing regimen

Launch Date

1.25340484E12
Primary
Phase III
663
Javlor

Approved Use

Javlor (vinflunine ditartrate) is indicated in monotherapy for the treatment of adult patients with advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing regimen

Launch Date

1.25340484E12
Primary
Phase III
663
Javlor

Approved Use

Javlor (vinflunine ditartrate) is indicated in monotherapy for the treatment of adult patients with advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing regimen

Launch Date

1.25340484E12
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics, tissue distribution and excretion of vinflunine.
2006 Apr-Jun
Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine.
2006 Nov
Anti-angiogenic, vascular-disrupting and anti-metastatic activities of vinflunine, the latest vinca alkaloid in clinical development.
2006 Nov
Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy.
2006 Nov 6
[NSCLC: update on second line therapy following ASCO 2007].
2007
Chemotherapy for metastatic or unresectable bladder cancer.
2007 Apr
American Society of Clinical Oncology--43rd annual meeting. Research into therapeutics: Part 2.
2007 Aug
Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma.
2007 Aug
Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP.
2007 Dec 25
CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes.
2007 Jan
Gateways to clinical trials.
2007 Jan-Feb
Therapy of metastatic bladder carcinoma.
2007 Jun
Development of a sensitive liquid chromatography method coupled with a tandem mass spectrometric detection for the clinical analysis of vinflunine and 4-O-deacetyl vinflunine in blood, urine and faeces.
2007 Jun 15
New agents for treatment of advanced transitional cell carcinoma.
2007 May
The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo.
2007 May 21
The evolving role of chemotherapy in advanced urothelial cancer.
2007 Oct
Gateways to clinical trials.
2007 Oct
Phase II study of vinflunine in malignant pleural mesothelioma.
2007 Oct 20
New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder.
2007 Sep
Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia.
2007 Sep 17
Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer.
2008 Apr
Murine leukemia P388 vinorelbine-resistant cell lines are sensitive to vinflunine.
2008 Aug
Novel therapies in genitourinary cancer: an update.
2008 Aug 11
Synthesis and biological evaluation of C-12' substituted vinflunine derivatives.
2008 Aug 15
Vinflunine in the treatment of bladder cancer.
2008 Dec
Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity.
2008 Dec 1
Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy.
2008 Jan 15
Antiangiogenic vinflunine affects EB1 localization and microtubule targeting to adhesion sites.
2008 Jul
Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro.
2008 Jul
Gateways to clinical trials. July-August 2008.
2008 Jul-Aug
Systemic treatments for mesothelioma: standard and novel.
2008 Jun
Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine.
2008 Jun
Vinflunine: discovery and synthesis of a novel microtubule inhibitor.
2008 Jun
Pharmacokinetics, metabolites, and preclinical safety of vinflunine.
2008 Jun
Potential mechanisms of resistance to microtubule inhibitors.
2008 Jun
Antitumor activity of vinflunine: effector pathways and potential for synergies.
2008 Jun
Introduction. The novel microtubule inhibitor vinflunine.
2008 Jun
Options for the treatment of patients with taxane-refractory metastatic breast cancer.
2008 Mar
Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy.
2008 Oct 13
Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting.
2008 Sep 15
Phase 2 study of single-agent IV vinflunine as third-line treatment of metastatic breast cancer after failure of anthracycline-/taxane-based chemotherapy.
2009 Aug
Systemic therapy of advanced urothelial cancer.
2009 Aug
Novel anti-tubulin cytotoxic agents for breast cancer.
2009 Feb
Gateways to clinical trials.
2009 Jan-Feb
Gateways to clinical trials.
2009 Mar
Gateways to clinical trials.
2009 May
Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa.
2009 May 22
What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?
2009 May 25
Second-line therapy in bladder cancer.
2009 Sep
Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study.
2009 Sep 15
Patents

Patents

JP2006519264A
58

Sample Use Guides

In Vivo Use Guide
The recommended dose is 320 mg/m² vinflunine as a 20 minute intravenous infusion every 3 weeks
Route of Administration: Intravenous
In Vitro Use Guide
IC50 values for inhibition of HeLa cell proliferation for vinflunine were 18 nM, similar to the concentrations that induced mitotic block at the metaphase/anaphase transition (38 nM)
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:14:19 UTC 2023
Edited
by admin
on Wed Jul 05 23:14:19 UTC 2023
Record UNII
33MG53C7XW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VINFLUNINE DITARTRATE
MI   USAN   WHO-DD  
USAN  
Official Name English
VINFLUNINE BITARTRATE
Common Name English
Vinflunine ditartrate [WHO-DD]
Common Name English
VINFLUNINE DITARTRATE [USAN]
Common Name English
VINFLUNINE DITARTRATE [MI]
Common Name English
4'-DEOXY-20',20'-DIFLUORO-8'-NORVINCALEUKOBLASTINE BITARTRATE
Common Name English
F-12158
Code English
BMS-710485
Code English
VINFLUNINE TARTRATE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67422
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
EMA ASSESSMENT REPORTS JAVLOR (AUTHORIZED: UROLOGIC NEOPLASMS)
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL2110725
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
USAN
TT-79
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
SMS_ID
100000092200
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
CAS
194468-36-5
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
EVMPD
SUB28421
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
PUBCHEM
16220212
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
CHEBI
90241
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
EPA CompTox
DTXSID80870081
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
FDA UNII
33MG53C7XW
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
MERCK INDEX
M11456
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY Merck Index
DRUG BANK
DBSALT002672
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
NCI_THESAURUS
C76266
Created by admin on Wed Jul 05 23:14:19 UTC 2023 , Edited by admin on Wed Jul 05 23:14:19 UTC 2023
PRIMARY
Related Record Type Details
Structure of VINFLUNINE
PARENT -> SALT/SOLVATE
Structure of TARTARIC ACID
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of VINFLUNINE
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