Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C45H54F2N4O8 |
Molecular Weight | 816.9291 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 10 / 10 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC[C@@]12C=CCN3CC[C@@]4([C@H]13)[C@@H](N(C)C5=CC(OC)=C(C=C45)[C@]6(C[C@@H]7C[C@H](C[N@@](C7)CC8=C6NC9=C8C=CC=C9)C(C)(F)F)C(=O)OC)[C@](O)([C@@H]2OC(C)=O)C(=O)OC
InChI
InChIKey=NMDYYWFGPIMTKO-KLCPSUAYSA-N
InChI=1S/C45H54F2N4O8/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/h9-14,19-20,26-27,36-38,48,55H,8,15-18,21-24H2,1-7H3/t26-,27+,36-,37+,38+,42+,43+,44-,45-/m0/s1
Molecular Formula | C45H54F2N4O8 |
Molecular Weight | 816.9291 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 9 / 9 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000983/WC500039604.pdfCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/18347163 | http://adisinsight.springer.com/drugs/800010899
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 |
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Target ID: CHEMBL2095182 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Javlor Approved UseJavlor (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 Date2009 |
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Primary | Javlor Approved UseJavlor (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 Date2009 |
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Primary | Javlor Approved UseJavlor (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 Date2009 |
PubMed
Title | Date | PubMed |
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Anti-vascular effects of vinflunine in the MAC 15A transplantable adenocarcinoma model. | 2001 Jan |
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Gemcitabine, paclitaxel, pemetrexed and other newer agents in urothelial and kidney cancers. | 2003 Jun 27 |
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Gateways to clinical trials. | 2003 Nov |
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Vinflunine potentiates the activity of cisplatin but not 5-fluorouracil in a transplantable murine adenocarcinoma model. | 2003 Nov-Dec |
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Gateways to clinical trials. | 2004 Apr |
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Modelling and simulation in the development and use of anti-cancer agents: an underused tool? | 2004 Dec |
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Highlights from the International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, And Clinical Applications, Philadelphia, PA, November 2005; ECCO 13--The European Cancer Conference, Paris, France, October 30-November 3, 2005. | 2005 Dec |
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[Vinflunine: a new anti-cancer fluorinated agent derived from Vinca-alkaloids]. | 2005 Jan |
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Gateways to clinical trials. | 2005 Oct |
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Vinflunine: a novel antitubulin agent in solid malignancies. | 2005 Oct |
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Pharmacokinetics, tissue distribution and excretion of vinflunine. | 2006 Apr-Jun |
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Gateways to clinical trials. | 2006 Mar |
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Update on tubulin-binding agents. | 2006 Mar |
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Phase I study of vinflunine administered as a 10-minute infusion on days 1 and 8 every 3 weeks. | 2006 May |
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Vinflunine -- an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study. | 2006 May 22 |
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Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine. | 2006 Nov |
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Phase II study of vinflunine in patients with metastatic renal cell carcinoma. | 2006 Sep |
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Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP. | 2007 Dec 25 |
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Gateways to clinical trials. | 2007 Jan-Feb |
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Gateways to clinical trials. | 2007 Oct |
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Systemic treatment for advanced (stage IIIb/IV) non-small cell lung cancer: more treatment options; more things to consider. Conclusion. | 2008 |
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Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. | 2008 Apr |
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Novel therapies in genitourinary cancer: an update. | 2008 Aug 11 |
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Synthesis and biological evaluation of C-12' substituted vinflunine derivatives. | 2008 Aug 15 |
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Vinflunine in the treatment of bladder cancer. | 2008 Dec |
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Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro. | 2008 Feb 29 |
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Gateways to clinical trials. | 2008 Jan-Feb |
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Gateways to clinical trials. July-August 2008. | 2008 Jul-Aug |
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Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management. | 2008 Jun |
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Clinical activity of vinflunine in transitional cell carcinoma of the urothelium and other solid tumors. | 2008 Jun |
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Antitumor activity of vinflunine: effector pathways and potential for synergies. | 2008 Jun |
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Introduction. The novel microtubule inhibitor vinflunine. | 2008 Jun |
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Options for the treatment of patients with taxane-refractory metastatic breast cancer. | 2008 Mar |
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Vinflunine: a new microtubule inhibitor agent. | 2008 Mar 15 |
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Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting. | 2008 Sep 15 |
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Gateways to clinical trials. | 2009 Jan-Feb |
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Gateways to clinical trials. | 2009 May |
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Second-line therapy in bladder cancer. | 2009 Sep |
Patents
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11408618
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
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Record UNII |
5BF646324K
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QL01CA05
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NCI_THESAURUS |
C932
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EMA ASSESSMENT REPORTS |
JAVLOR (AUTHORIZED: CARCINOMA, TRANSITIONAL CELL, UROLOGIC NEOPLASM)
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L01CA05
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C67422
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