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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
Structure of VINFLUNINE

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

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Primary
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

PubMed

TitleDatePubMed
Anti-vascular effects of vinflunine in the MAC 15A transplantable adenocarcinoma model.
2001 Jan
Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine.
2001 Jul
Vinflunine, a second generation novel Vinca Alkaloid with a distinctive pharmacological profile, now in clinical development and prospects for future mitotic blockers.
2001 Sep
Modifications in the "upper" velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities.
2001 Sep
Model of chemotherapy-induced myelosuppression with parameter consistency across drugs.
2002 Dec 15
Novel aspects of natural and modified vinca alkaloids.
2002 Jan
Characterization of cell death induced by vinflunine, the most recent Vinca alkaloid in clinical development.
2002 Jan 7
Gateways to clinical trials.
2003 Nov
Vinflunine potentiates the activity of cisplatin but not 5-fluorouracil in a transplantable murine adenocarcinoma model.
2003 Nov-Dec
Modelling and simulation in the development and use of anti-cancer agents: an underused tool?
2004 Dec
Gateways to clinical trials.
2004 Jan-Feb
Gateways to clinical trials.
2004 Jun
Vinflunine.
2004 Sep
[Acronycine revisited: development of benzo[b]acronycine antitumor agents].
2005 Jan
[Vinflunine: a new anti-cancer fluorinated agent derived from Vinca-alkaloids].
2005 Jan
Gateways to clinical trials.
2005 Oct
Vinflunine: a novel antitubulin agent in solid malignancies.
2005 Oct
Cell cycle effects of vinflunine, the most recent promising Vinca alkaloid, and its interaction with radiation, in vitro.
2006 Aug
Determination of vinflunine in rat plasma by liquid chromatography-electrospray ionization mass spectrometry for a pharmacokinetic study.
2006 Jun 7
Gateways to clinical trials.
2006 Mar
A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.
2006 May 22
Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine.
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
Phase II study of vinflunine in patients with metastatic renal cell carcinoma.
2006 Sep
Vinflunine, a novel microtubule inhibitor, suppresses calmodulin interaction with the microtubule-associated protein STOP.
2007 Dec 25
Gateways to clinical trials.
2007 Jan-Feb
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
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
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
Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.
2008 Feb 29
Exploring the mechanisms of action of the novel microtubule inhibitor vinflunine.
2008 Jun
Clinical activity of vinflunine in transitional cell carcinoma of the urothelium and other solid tumors.
2008 Jun
Vinflunine: discovery and synthesis of a novel microtubule inhibitor.
2008 Jun
Potential mechanisms of resistance to microtubule inhibitors.
2008 Jun
Antitumor activity of vinflunine: effector pathways and potential for synergies.
2008 Jun
Newer cytotoxic agents: attacking cancer broadly.
2008 Mar 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 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
Patents

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
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 Sat Dec 16 17:40:39 GMT 2023
Edited
by admin
on Sat Dec 16 17:40:39 GMT 2023
Record UNII
5BF646324K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VINFLUNINE
EMA EPAR   INN   MART.   MI   WHO-DD  
INN  
Official Name English
VINFLUNINE [MI]
Common Name English
VINFLUNINE [EMA EPAR]
Common Name English
4'-DEOXY-20',20'-DIFLUORO-8'-NORVINCALEUCOBLASTINE
Common Name English
vinflunine [INN]
Common Name English
VINFLUNINE [MART.]
Common Name English
Vinflunine [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-VATC QL01CA05
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
NCI_THESAURUS C932
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
EMA ASSESSMENT REPORTS JAVLOR (AUTHORIZED: CARCINOMA, TRANSITIONAL CELL, UROLOGIC NEOPLASM)
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
WHO-ATC L01CA05
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
NCI_THESAURUS C67422
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID30936722
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
MERCK INDEX
m11456
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY Merck Index
SMS_ID
100000079091
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
EVMPD
SUB00063MIG
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
CAS
162652-95-1
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
ChEMBL
CHEMBL2110725
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
DRUG CENTRAL
3644
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
DRUG BANK
DB11641
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
WIKIPEDIA
Vinflunine
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
INN
7499
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
PUBCHEM
10629256
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
FDA UNII
5BF646324K
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
MESH
C111217
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
CHEBI
90241
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
NCI_THESAURUS
C61564
Created by admin on Sat Dec 16 17:40:39 GMT 2023 , Edited by admin on Sat Dec 16 17:40:39 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY