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
[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=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 | 8 / 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 |
---|---|---|---|
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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Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. | 2001 Jul |
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Vinflunine, a second generation novel Vinca Alkaloid with a distinctive pharmacological profile, now in clinical development and prospects for future mitotic blockers. | 2001 Sep |
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Modifications in the "upper" velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities. | 2001 Sep |
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Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. | 2002 Dec 15 |
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Novel aspects of natural and modified vinca alkaloids. | 2002 Jan |
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Characterization of cell death induced by vinflunine, the most recent Vinca alkaloid in clinical development. | 2002 Jan 7 |
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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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Modelling and simulation in the development and use of anti-cancer agents: an underused tool? | 2004 Dec |
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Gateways to clinical trials. | 2004 Jan-Feb |
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Gateways to clinical trials. | 2004 Jun |
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Vinflunine. | 2004 Sep |
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[Acronycine revisited: development of benzo[b]acronycine antitumor agents]. | 2005 Jan |
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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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Cell cycle effects of vinflunine, the most recent promising Vinca alkaloid, and its interaction with radiation, in vitro. | 2006 Aug |
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Determination of vinflunine in rat plasma by liquid chromatography-electrospray ionization mass spectrometry for a pharmacokinetic study. | 2006 Jun 7 |
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Gateways to clinical trials. | 2006 Mar |
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A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. | 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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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 |
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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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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 |
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New agents for treatment of advanced transitional cell carcinoma. | 2007 May |
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Gateways to clinical trials. | 2007 Oct |
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Phase II study of vinflunine in malignant pleural mesothelioma. | 2007 Oct 20 |
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New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder. | 2007 Sep |
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Murine leukemia P388 vinorelbine-resistant cell lines are sensitive to vinflunine. | 2008 Aug |
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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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Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity. | 2008 Dec 1 |
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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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Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine. | 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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Vinflunine: discovery and synthesis of a novel microtubule inhibitor. | 2008 Jun |
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Potential mechanisms of resistance to microtubule inhibitors. | 2008 Jun |
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Antitumor activity of vinflunine: effector pathways and potential for synergies. | 2008 Jun |
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Newer cytotoxic agents: attacking cancer broadly. | 2008 Mar 15 |
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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 |
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Systemic therapy of advanced urothelial cancer. | 2009 Aug |
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Novel anti-tubulin cytotoxic agents for breast cancer. | 2009 Feb |
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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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Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa. | 2009 May 22 |
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What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine? | 2009 May 25 |
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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admin
on
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Record UNII |
5BF646324K
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Record Status |
Validated (UNII)
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WHO-VATC |
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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