General
Preferred name
vinorelbine
Synonyms
VINORELBIN DITARTRATE ()
Vinorelbine Tartrate ()
Vinorelbine ()
VINORELBINE BASE ()
Nor-5'-anhydrovinblastine ditartrate ()
KW-2307 ()
Vinorelbine ditartrate ()
Navelbine tartrate ()
KW-2307 base ()
Navelbine ()
Vinorelbine (tartrate) ()
Vinorelbine (Navelbine) ()
Biovelbin ()
Navelbine ditartrate ()
Vinorelbine (ditartrate) ()
NSC-760087 ()
Vinorelbine Base ()
Navelbin ()
TLC178 ()
Vinorelbine liposomal ()
TLC-178 ()
Vinorelbine Ditartarate ()
Liposomal vinorelbine tartrate ()
Vinorelbine tartrate (1:2) ()
Vinorelbine (as tartrate) ()
Vinorelbine (tartrate) ()
P&D ID
PD039019
CAS
125317-39-7
71486-22-1
Tags
nuisance
natural product
drug
available
Approved by
FDA
First approval
1994
Drug Status
investigational
approved
Drug indication
Antineoplastic
Solid tumour/cancer
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Vinorelbine is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells [L2007].
INDICATION
Vinorelbine tartrate is indicated for adults in the treatment of advanced non-small cell lung cancer (NSCLC), as a single therapy or in combination with other chemotherapeutic drugs [L1998].; ; Used in relapsed or refractory Hodgkin lymphoma, in combination with other chemotherapy agents [L2011].; ; For the treatment of desmoid tumor or aggressive fibromatosis, in combination with methotrexate [L2011].; ; For the treatment of recurrent or metastatic squamous cell head and neck cancer [L2011].; ; For the treatment of recurrent ovarian cancer [L2011].; ; For the treatment of metastatic breast cancer, in patients previously treated with anthracyline and/or taxane therapy [L2011].; ; For the treatment of HER2-positive, trastuzumab-resistant, advanced breast cancer in patients previously treated with a taxane, in combination with trastuzumab and everolimus [L2011].;
ROE
Vinorelbine undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans [L1998].; ; Urinary excretion of unchanged drug accounts for less than 20% of an intravenous dose, with fecal elimination accounting for an additional 30% to 60% [A32354].; ; After intravenous administration of radioactive vinorelbine, approximately 18% and 46% of administered radioactivity was recovered in urine and feces, respectively [L2002].
METABOLISM
Vinorelbine undergoes substantial hepatic elimination in humans. Two metabolites of vinorelbine have been identified in human blood, plasma, and urine; vinorelbine N-oxide and deacetylvinorelbine. Deacetylvinorelbine has been demonstrated to be the primary metabolite of vinorelbine in humans, and has been shown to possess antitumor activity similar to vinorelbine [L2005], [L2006].; ; Vinorelbine is metabolized into two other minor metabolites, 20'-hydroxyvinorelbine and vinorelbine 6'-oxide [L2006].; ; Therapeutic doses of vinorelbine (30 mg/m2) yield very small, if any, quantifiable levels of either metabolite in blood or urine. The metabolism of vinorelbine is mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily [L2004], [A32354].; ; As the liver provides the main route for metabolism of the drug, patients with hepatic impairment may demonstrate increased toxicity with standard dosing, however, there are no available data on this. Likewise, the contribution of cytochrome P450 enzyme action to vinorelbine metabolism has potential implications in patients receiving other drugs metabolized by this route [L2007].
ABSORPTION
Vinorelbine is rapidly absorbed with peak serum concentration reached within 2 hours [L1998].; ; Vinorelbine is highly bound to platelets and lymphocytes and is also bound to alpha 1-acid glycoprotein, albumin, and lipoproteins [A32354].
DESCRIPTION
Vinorelbine is an anti-mitotic chemotherapy drug.
(GtoPdb)
MOA
Vinca alkaloids are structurally similar compounds composed of two multi-ringed units, _vindoline_, and _catharanthine_. _Vinorelbine tartrate_ is a vinca alkaloid in which the catharanthine component is the target of structural modification [L2005], [L2006].; ; This structural modification contributes to unique pharmacologic properties.The antitumor activity of vinorelbine tartrate is believed to be owed to the inhibition of mitosis at metaphase via its interaction with tubulin [L1998].; ; Vinorelbine is a mitotic spindle poison that interferes with chromosomal segregation during mitosis, also known as cell division. It pauses cells at the _G2/M_ phases, when present at concentrations close to the half maximal inhibitory concentration (IC50). Microtubules, which are derived from polymers of tubulin, are the main target of vinorelbine. ; ; The chemical modification used to produce vinorelbine allows for the opening of the eight-member catharanthine ring with the formation of both a covalent and reversible bond with tubulin [L2007].; ; The relative contribution of different microtubule-associated proteins in the production of tubulin vary between neural tissue and proliferating cells and this has important functional implications. The ability of vinorelbine to bind specifically to mitotic rather than other microtubules has been shown and may suggest that neurotoxicity is less likely to be a problem than with the molecular mechanism of action [L2007]. ; ; As with other anti-microtubule agents, vinorelbine is known to contribute apoptosis in malignant cells. The exact mechanisms by which this process occurs are complex and many details are yet to be elucidated. The disarray of the microtubule structure has a number of effects, including the induction of tumor suppressor gene _p53_ and activation/inactivation of a number of protein kinases involved in essential signaling pathways, including _p21 WAF1/CIP1_ and _Ras/Raf_, _PKC/PKA_. These molecular changes lead to phosphorylation and consequently inactivation of the apoptosis inhibitor _Bcl2_. This, in turn, results in a decrease in the formation of heterodimers between _Bcl2_ and the pro-apoptotic gene _BAX_, stimulating the sequence of cell apoptosis [L2007].; ; Vinorelbine tartrate also possibly interferes with amino acid, cyclic AMP and glutathione metabolism, calmodulin-dependent Ca++-transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis [L1998].;
DESCRIPTION
Inhibitor of macrophage migration inhibitory factor (MIF); suicide substrate
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
677
Organisms
1
Compound Sets
24
AdooQ Bioactive Compound Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
Nuisance compounds in cellular assays
Other bioactive compounds
ReFrame library
Tocris Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
62
Molecular Weight
778.39
Hydrogen Bond Acceptors
11
Hydrogen Bond Donors
2
Rotatable Bonds
7
Ring Count
9
Aromatic Ring Count
3
cLogP
4.75
TPSA
133.87
Fraction CSP3
0.53
Chiral centers
9.0
Largest ring
8.0
QED
0.2
Structural alerts
1
Tubulin modulation
Nuisance compounds in cellular assays
Related compounds
Custom attributes
(extracted from source data)
Target
Microtubule/Tubulin
Autophagy
Tubulin
Tubulin ?? chain
TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBB4B, TUBB6, TUBB8
Pathway
Cell Cycle/DNA Damage
cytoskeleton
Cytoskeletal Signaling
Primary Target
Microtubules
MOA
Microtubule Associated inhibitor
Antimitotic Drugs
Tubulin Polymerization Inhibitors
tubulin polymerization inhibitor
Member status
virtual
Indication
non-small cell lung cancer (NSCLC)
Biosynthetic Origin
Alkaloid, Terpenoid
Therapeutic Indication
Anticancer
Therapeutic Class
Anticancer Agents
Source data
