Vinflunine

Chemical compound

EU EMA: by INN

Routes of
administrationIntravenousATC code

L01CA05 (WHO)

Legal statusLegal status

EU: Rx-only^[1]
In general: ℞ (Prescription only)

Identifiers

IUPAC name

methyl (2β,3β,4β,5α,12β,19α)- 4-(acetyloxy)- 15-[(4R,6R,8S)- 4-(1,1-difluoroethyl)- 8-(methoxycarbonyl)- 1,3,4,5,6,7,8,9-octahydro- 2,6-methanoazecino[4,3-b]indol- 8-yl]- 3-hydroxy- 16-methoxy- 1-methyl- 6,7-didehydroaspidospermidine- 3-carboxylate

CAS Number

162652-95-1^Y

PubChem CID

10629256

DrugBank

DB11641^Y

ChemSpider

8804619^N

UNII

5BF646324K

ChEBI

CHEBI:90241^N

ChEMBL

ChEMBL2110725^N

CompTox Dashboard (EPA)

DTXSID30936722

Chemical and physical dataFormulaC₄₅H₅₄F₂N₄O₈Molar mass816.944 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

CC[C@@]12C=CCN3[C@@H]1[C@]4(CC3)[C@H]([C@]([C@@H]2OC(=O)C)(C(=O)OC)O)N(C5=CC(=C(C=C45)[C@]6(C[C@H]7C[C@H](CN(C7)CC8=C6NC9=CC=CC=C89)C(C)(F)F)C(=O)OC)OC)C

InChI

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^N
Key:NMDYYWFGPIMTKO-KLCPSUAYSA-N^N

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Vinflunine (INN, trade name Javlor) is a novel fluorinated vinca alkaloid derivative^[2] undergoing research for the treatment of bladder cancer. It was originally discovered by the team of the Professor Jean-Claude Jacquesy (UMR CNRS 6514 – Poitiers University),^[3] developed by Laboratoires Pierre Fabre and was licensed to Bristol-Myers Squibb for development in certain countries, including the United States.

On November 23, 2007, Pierre Fabre Medicament and Bristol-Myers Squibb announced that they were terminating their license agreement for the development of vinflunine, and that Pierre Fabre were continuing "discussions with regulatory authorities and plan to file for the registration of vinflunine for bladder cancer in the first quarter of 2008."^[4]

Approvals and indications

As of 2012^[update], vinflunine was registered for use in Australia for "advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum containing regimen," but is not covered under the Pharmaceutical Benefits Scheme.^[5]

As of 2016^[update], vinflunine was the only commercially-approved agent in some countries for salvage therapy of urothelial carcinoma, (with approval based on the results of a phase III trial), with a reported median OS of about 6 months.^[6]^[7]

Clinical trials

It has undergone a phase III clinical trial for advanced transitional cell carcinoma of the urothelial tract.^[7]

References

^ "Javlor EPAR". European Medicines Agency (EMA). Retrieved 2 January 2021.
^ Kruczynski A, Barret JM, Etiévant C, Colpaert F, Fahy J, Hill BT (March 1998). "Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid". Biochemical Pharmacology. 55 (5): 635–48. doi:10.1016/S0006-2952(97)00505-4. PMID 9515574.
^ Fahy J, Duflos A, Ribet JP, Jacquesy JC, Berrier C, Jouannetaud MP, Zunino F (1997). "Vinca Alkaloids in Superacidic Media: A Method for Creating a New Family of Antitumor Derivatives". J. Am. Chem. Soc. 119 (36): 8576–8577. doi:10.1021/ja971864w.
^ "Bristol-Myers Squibb and Pierre Fabre Provide Update On Vinflunine Development Status" (Press release). Bristol-Myers Squibb. November 23, 2007. Archived from the original on May 28, 2008. Retrieved June 27, 2008.
^ "Vinflunine, solution concentration for I.V. infusion, 50 mg in 2 mL and 250 mg in 10 mL (as ditartrate), Javlor® – November 2011". Pharmaceutical Benefits Scheme. March 16, 2012. Retrieved June 22, 2017.
^ Sonpavde G (June 2016). "Systemic Therapy for Urothelial Carcinoma: Is a Renaissance Around the Corner?". Oncology. 30 (6): 580–3, 588. PMID 27306713.
^ ^a ^b Bellmunt J, Théodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. (September 2009). "Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract". Journal of Clinical Oncology. 27 (27): 4454–61. doi:10.1200/JCO.2008.20.5534. PMID 19687335.

External links

"Vinflunine". Drug Information Portal. U.S. National Library of Medicine.

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vindesine Vinflunine^§ Vinorelbine^#)
Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel^# Larotaxel Ortataxel^† Paclitaxel^# Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate^# Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Pemetrexed Raltitrexed)
Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Mercaptopurine^# Tioguanine^#)
Pyrimidine	Thymidylate synthase inhibitor (Capecitabine^# Carmofur Doxifluridine Floxuridine Fluorouracil^# Tegafur (+gimeracil/oteracil)) DNA polymerase inhibitor (Cytarabine^# +daunorubicin) Ribonucleotide reductase inhibitor (Gemcitabine^#) Hypomethylating agent (Azacitidine Decitabine)
Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide^#)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Belotecan Camptothecin Cositecan^† Etirinotecan pegol^† Exatecan Gimatecan Irinotecan^# Lurtotecan^‡ Rubitecan^‡ Silatecan^§ Topotecan)
II	Podophyllum (Etoposide^# Teniposide)
II+Intercalation	Anthracyclines (Aclarubicin Amrubicin^† Daunorubicin^# (+cytarabine) Doxorubicin^# Epirubicin Idarubicin Pirarubicin Valrubicin Zorubicin) Anthracenediones (Mitoxantrone Losoxantrone Pixantrone) Amsacrine Bisantrene Crisnatol Menogaril^§

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Bendamustine^# Chlormethine Cyclophosphamide^# (Ifosfamide^# Trofosfamide) Chlorambucil^# Melphalan (Melphalan flufenamide) Prednimustine Uramustine Nitrosoureas: Carmustine Fotemustine Lomustine (Semustine) Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone Thiotepa Triaziquone Triethylenemelamine
Platinum-based	Carboplatin^# Cisplatin^# Dicycloplatin Nedaplatin Oxaliplatin^# Satraplatin
Nonclassical	Altretamine Hydrazines (Procarbazine^#) Etoglucid Mitobronitol Pipobroman Triazenes (Dacarbazine^# Mitozolomide^§ Temozolomide)
Intercalation	Streptomyces (Dactinomycin^# Bleomycin^# Mitomycins Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Abemaciclib Alvocidib^† Palbociclib Ribociclib Seliciclib^†) PrI Bortezomib Carfilzomib Oprozomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Fuzuloparib) Niraparib +abiraterone acetate Olaparib Rucaparib) HDAC (Belinostat Entinostat Panobinostat Romidepsin Vorinostat) PIKI (Pi3K) (Alpelisib Copanlisib Duvelisib Idelalisib Umbralisib^‡)
Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)
Other/ungrouped	Adagrasib Aflibercept Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Axicabtagene ciloleucel Belzutifan Bexarotene Brexucabtagene autoleucel Celecoxib Ciltacabtagene autoleucel Demecolcine Denileukin diftitox Elesclomol^§ Elsamitrucin Enasidenib Epacadostat Eribulin Estramustine phosphate Glasdegib Idecabtagene vicleucel Ivosidenib Lifileucel Lonidamine Lucanthone Lurbinectedin Mitoguazone Mitotane Oblimersen^† Omacetaxine mepesuccinate Plitidepsin Retinoids (Alitretinoin Tretinoin^#) Selinexor Sitimagene ceradenovec Sotorasib Tagraxofusp Talimogene laherparepvec Tazemetostat Tebentafusp Tiazofurine Tigilanol tiglate Tisagenlecleucel Trabectedin Veliparib Venetoclax Verdinexor Vosaroxin