VINFLUNINE DITARTRATE

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 Search

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
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000983/WC500039604.pdf
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

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9515574 \| https://www.ncbi.nlm.nih.gov/pubmed/18347163	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Transitional cell carcinoma 2 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000983/WC500039604.pdf	Primary	Approved 8429	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 2009
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800010899	Primary	Phase III 656	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 2009
Head and neck cancer 50 Sources: http://adisinsight.springer.com/drugs/800010899	Primary	Phase III 656	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 2009

PubMed

Title	Date	PubMed
[NSCLC: update on second line therapy following ASCO 2007].	2007	18157591
American Society of Clinical Oncology--43rd annual meeting. Research into therapeutics: Part 2.	2007 Aug	17665321
Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma.	2007 Aug	17631996
Evolving nonendocrine therapeutic options for metastatic breast cancer: how adjuvant chemotherapy influences treatment.	2007 Dec	18269773
Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP.	2007 Dec 25	18052208
Therapy of metastatic bladder carcinoma.	2007 Jun	17591811
The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo.	2007 May 21	17473826
The evolving role of chemotherapy in advanced urothelial cancer.	2007 Oct	18685360
Gateways to clinical trials.	2007 Oct	18040531
Phase II study of vinflunine in malignant pleural mesothelioma.	2007 Oct 20	17947722
New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder.	2007 Sep	17762632
Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia.	2007 Sep 17	17726463
Systemic treatment for advanced (stage IIIb/IV) non-small cell lung cancer: more treatment options; more things to consider. Conclusion.	2008	18263773
Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer.	2008 Apr	18410797
Vinflunine: clinical perspectives of an emerging anticancer agent.	2008 Apr	18363522
Murine leukemia P388 vinorelbine-resistant cell lines are sensitive to vinflunine.	2008 Aug	18071633
Novel therapies in genitourinary cancer: an update.	2008 Aug 11	18694493
Synthesis and biological evaluation of C-12' substituted vinflunine derivatives.	2008 Aug 15	18653334
Vinflunine in the treatment of bladder cancer.	2008 Dec	19337431
Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity.	2008 Dec 1	19047161
Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.	2008 Feb 29	18312675
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	18087289
Gateways to clinical trials.	2008 Jan-Feb	18389098
Antiangiogenic vinflunine affects EB1 localization and microtubule targeting to adhesion sites.	2008 Jul	18645018
Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro.	2008 Jul	17899084
Gateways to clinical trials. July-August 2008.	2008 Jul-Aug	18850047
Systemic treatments for mesothelioma: standard and novel.	2008 Jun	18770046
Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management.	2008 Jun	18567992
Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine.	2008 Jun	18538179
Clinical activity of vinflunine in transitional cell carcinoma of the urothelium and other solid tumors.	2008 Jun	18538178
Vinflunine: discovery and synthesis of a novel microtubule inhibitor.	2008 Jun	18538177
Pharmacokinetics, metabolites, and preclinical safety of vinflunine.	2008 Jun	18538176
Potential mechanisms of resistance to microtubule inhibitors.	2008 Jun	18538175
Antitumor activity of vinflunine: effector pathways and potential for synergies.	2008 Jun	18538174
Introduction. The novel microtubule inhibitor vinflunine.	2008 Jun	18538173
Options for the treatment of patients with taxane-refractory metastatic breast cancer.	2008 Mar	18637401
Vinflunine: a new microtubule inhibitor agent.	2008 Mar 15	18347163
Newer cytotoxic agents: attacking cancer broadly.	2008 Mar 15	18347161
Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy.	2008 Oct 13	18644768
Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting.	2008 Sep 15	18629841
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	19487917
Systemic therapy of advanced urothelial cancer.	2009 Aug	19408129
Novel anti-tubulin cytotoxic agents for breast cancer.	2009 Feb	19192956
Gateways to clinical trials.	2009 Jan-Feb	19357798
Gateways to clinical trials.	2009 Mar	19455266
Gateways to clinical trials.	2009 May	19557204
Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa.	2009 May 22	19463163
What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?	2009 May 25	19467159
Second-line therapy in bladder cancer.	2009 Sep	19550334
Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study.	2009 Sep 15	19536904

Patents

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 `Fri Dec 15 15:45:44 GMT 2023` Edited by `admin` on `Fri Dec 15 15:45:44 GMT 2023`
Record UNII	33MG53C7XW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VINFLUNINE DITARTRATE

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