125317-39-7 Usage
Description
Vinorelbine tartrate, also known as Navelbine, is an antineoplastic agent and a derivative of vinblastine. It was first marketed in 1989 in France and is characterized by its pale yellow or white crystalline powder form. Vinorelbine tartrate is a cycle-specific drug that works by binding to tubulin, disrupting microtubule formation during cell mitosis. It is highly lipophilic, allowing for rapid uptake into cells, including lung tissue, where its concentration is significantly higher than in plasma. The drug is highly protein-bound and metabolized by CYP3A, with a major metabolite being the 4-O-desacetyl derivative. It is eliminated primarily through the bile, with some excretion in the urine. The elimination half-life of vinorelbine tartrate is between 27 to 43 hours.
Uses
Used in Oncology:
Vinorelbine tartrate is used as an antineoplastic agent for the treatment of various types of cancer. It is particularly effective against non-small cell lung cancer (NSCLC) and has been used to treat breast cancer, ovarian cancer, head and neck squamous cell carcinoma, and leukemia. Additionally, it has a strong inhibitory effect on small cell lung cancer, colon cancer, brain tumors, and malignant melanoma.
Used in Drug Delivery Systems:
Vinorelbine tartrate has been incorporated into drug delivery systems to enhance its therapeutic outcomes and bioavailability. These systems aim to improve the drug's delivery to cancer cells, overcoming limitations associated with its use as a standalone treatment.
Toxicities and Side Effects:
The primary dose-limiting toxicity of vinorelbine tartrate is myelosuppression, which can manifest as neutropenia. It is essential to monitor patients' neutrophil counts before and during therapy to reduce the risk of infection. Other toxicities include nausea and vomiting, elevation of liver function tests, alopecia, generalized fatigue, and inappropriate secretion of antidiuretic hormone. Neurotoxicity is less common with vinorelbine tartrate compared to other vinca alkaloids due to its decreased affinity for axonal microtubules.
Pharmacological effects
Vinorelbine tartrate is the tartrate form of vinorelbine ,it is a semi-synthetic? vincristine compound, it belongs to M phase specific drugs, mechanism of action is similar to vincristine . Mainly it , by selectively blocking mitotic cell tubulin polymerization to form microtubule and? inducing tubulin depolymerization , impedes spindle microtubules,and it makes cell division stop? in the middle, and it has few effect on the synthetic tubulin in the shaft of nerve cells. Since NVB affinity for axonal microtubules is poor, only when there is a high concentration of it ,it has effect on axonal , so it has the lower neurotoxicity than other vincristine drugs,and it? has a greater therapeutic index. Human pharmacokinetics of vinorelbine show that after intravenous administration there is a three-compartment model, the volume? of distribution is large , PPB is up to 50% to 80%, plasma clearance rate is high, the terminal elimination phase T1/2 is 40 h, it has a rapid tissue distribution, concentration in tissues is significantly higher than vincristine (VCR), vindesine (VDS). Plasma clearance is 0.8 L/(kg ? h),it is mainly through biliary secretion, and it is excreted with the feces, urine excretion accounts for 10% to 15%.It has a higher efficacy and less adverse reactions of the nervous system.
Clinical evaluation
Numerous clinical studies have shown that vinorelbine is one of the most effective drugs for the treatment of non-small cell lung cancer and breast cancer, single agent response rate is 14% to 35% and 30% to 60% respectively. And DDP combination chemotherapy in NSCLC and with doxorubicin combination therapy of breast cancer, efficiency is up to 30% to 50% and 50% to 77%, respectively. It has a good effect on ovarian cancer, malignant lymphoma, head and neck cancer, esophageal cancer.
Adverse reactions
Vinorelbine hematologic toxicity is dose-limiting , mainly it is neutropenia, which mostly restore? within 7d, it has a certain influence on red blood cells , thrombocytopenia and anemia incidence is less than 2%.
Neurotoxicity mainly performs as tendon reflexes (about 25%), occasional paresthesia, few patients may have gastrointestinal autonomic nerve paralysis induced constipation (17%~41%),? paralytic ileus is rare? , 2% 6% of the patients suffer finger (toe) numb, but the incidence is much lower than the VCR and VDS.
Incidence of gastrointestinal side effects is less than 10%. Occasionally, nausea, vomiting, dyspnea, and bronchospasm, often occur in a few minutes or several hours after treatment . Alopecia incidence is less than 10%.
Vinorelbine drug extravasation into the surrounding tissue can cause burning, injection site phlebitis, local tissue necrosis, ulceration, cellulitis.
Myelosuppression is dose-limiting toxicity. 3 to 5 days after the medication, transient myelosuppression can occur, usually it can recover within 10 days, attention should be paid to prevent infection. Neurotoxicity is visible.
Biological Activity
Selective mitotic microtubule antagonist that exhibits > 20 fold selectivity over axonal microtubules. Inhibits proliferation of multiple human tumor cell lines (IC 50 = 1.25 nM in HeLa cells) and blocks metaphase/anaphase transition by suppression of microtubule dynamics (IC 50 = 3.8 nM). Reduces spindle length by 29% and inhibits microtubule polymerization at micromolar concentrations.
Biochem/physiol Actions
Vinorelbine is a potent anti-mitotic, anti-tumor agent. Vinorelbine inhibits microtubule assembly. Low neurotoxicity is related to its higher affinity for mitotic microtubules than for axonal microtubules.
Check Digit Verification of cas no
The CAS Registry Mumber 125317-39-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,5,3,1 and 7 respectively; the second part has 2 digits, 3 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 125317-39:
(8*1)+(7*2)+(6*5)+(5*3)+(4*1)+(3*7)+(2*3)+(1*9)=107
107 % 10 = 7
So 125317-39-7 is a valid CAS Registry Number.
InChI:InChI=1/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1
