Metabolism / Metabolites
Liver Liver Half-life: 24 hours. Biological Half-life 24 hours.

Toxicity Summary
Vinpocetine arrests cells in metaphase by inhibiting the mitotic function of tubulin. This drug is specific for the S phase of the cell cycle.

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Protein Binding
65-75% Toxicity Data
LD50: 4 mg/kg (mice) Interactions Vinpocetine-induced leukopenia and/or thrombocytopenia may be exacerbated if the patient is receiving other medications concurrently or recently, especially if these medications/medications causing blood disorders/have the same effect; the dose of vinpocetine should be adjusted according to blood cell counts if necessary. Additive myelosuppression may occur, including severe dermatitis and/or mucositis; dose reduction may be necessary when using two or more myelosuppressants (including radiation) concurrently or sequentially. Acute dyspnea and severe bronchospasm have been reported with combination therapy (including vinca alkaloids); this reaction may occur within minutes or hours after injection of vinca alkaloids. Neurotoxicity may occur early in treatment and may be more severe if used concomitantly with other neurotoxic drugs. For more complete data on interactions of vindesine (7 drugs in total), please visit the HSDB record page.

[1]. Vinca alkaloids. Cancer Chemother Biol Response Modif. 1991;12:67-73.

Vindesine is a vinca alkaloid belonging to the methyl ester, organic heterotetracyclic, organic heteropentacyclic, tertiary alcohol, tertiary amino, and primary carboxamide classes. It is an antitumor drug, its function related to vinblastine. Vindesine derivatives possess antitumor activity. The main side effects are myelosuppression and neurotoxicity. Vindesine is widely used in chemotherapy regimens (antitumor combination chemotherapy regimens). Vindesine is a synthetic derivative of the naturally occurring vinca alkaloid, vinblastine. Vindesine binds to and stabilizes tubulin, thereby interfering with tubulin polymerization, preventing the formation of the mitotic spindle and cell division; treated cells cannot undergo mitosis and are arrested at metaphase. The drug also interferes with macromolecule synthesis. (NCI04) Vindesine is only found in individuals who have used or taken this drug. It is a vinblastine derivative with antitumor activity. The main side effects are myelosuppression and neurotoxicity. Vindesine is widely used in chemotherapy regimens (antitumor combination chemotherapy regimens). Vindesine arrests cells in metaphase of mitosis by inhibiting the mitotic function of tubulin. This drug is specific to the S phase of the cell cycle. It is a vinblastine derivative with antitumor activity. The main side effects are myelosuppression and neurotoxicity. Vindesine is widely used in chemotherapy regimens (antitumor combination chemotherapy regimens). Drug Indications Used to treat acute leukemia, malignant lymphoma, Hodgkin's lymphoma, acute polycythemia, and acute pancytosis. Mechanism of Action Vindesine arrests cells in metaphase of mitosis by inhibiting the mitotic function of tubulin. This drug is specific to the S phase of the cell cycle. Vindesine can arrest cells in metaphase of mitosis. In in vitro studies, when the dose is sufficient to arrest 10% to 15% of cells in mitosis, Vindesine is three times more potent than Vindesine and almost ten times more potent than vinblastine. When the dose is sufficient to arrest 40% to 50% of cells in the mitotic phase, vindesine and Vindesine are roughly equivalent in potency. Unlike Vindesine, vindesine produces very few late-stage cells. Vindesine has been shown to be effective in patients who have relapsed after multidrug therapy, including Vindesine. Toxic doses of vindesine administered to male and female rats did not affect their fertility.

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Therapeutic Uses
Vindesine is indicated for the treatment of juvenile acute lymphoblastic leukemia resistant to Vindesine.
/US Product Label Includes/
Vindesine is indicated for the treatment of non-oat cell lung cancer. /US Product Label Includes/

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Drug Warnings
Pregnant women must weigh the risks and benefits before using vindesine. It is generally recommended to avoid the use of anti-tumor drugs during pregnancy, especially in combination with chemotherapy, particularly in the first trimester. Although information is limited due to the relatively small number of cases of anti-tumor drug use during pregnancy, the mutagenicity, teratogenicity, and carcinogenicity of these drugs should still be considered. Other risks to the fetus include adverse reactions common in adults. Appropriate studies conducted to date have not identified any pediatric-specific problems limiting the use of vindesine in children. Strict adherence to the recommended dosing regimen is essential. Long-term, low-dose daily use of vindesine for the treatment of childhood acute lymphoblastic leukemia is not recommended, even if the resulting weekly dose may be similar to the recommended dose. Such regimens offer little or no therapeutic benefit and increase the incidence of adverse reactions. The myelosuppressive effects of vindesine may lead to an increased incidence of microbial infections, delayed wound healing, and gingival bleeding. Dental procedures should be completed before the start of treatment whenever possible, or postponed until blood cell counts have returned to normal. Patients should be instructed to maintain good oral hygiene, including careful use of regular toothbrushes, dental floss, and toothpicks.

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Pharmacodynamics
Vindesine is indicated for the treatment of childhood acute lymphoblastic leukemia and non-oat cell lung cancer resistant to Vindesine. Vindesine causes cell arrest at metaphase of mitosis. In in vitro studies, when doses were sufficient to arrest mitosis in 10% to 15% of cells, vindesine's ability to induce mitosis was three times that of Vindesine and almost ten times that of vinblastine. When doses were sufficient to arrest mitosis in 40% to 50% of cells, the potency of vindesine and Vindesine was roughly equivalent. Unlike vinblastine, vindesine produces very few late-stage cells. Vindesine has been shown to be effective in patients who have relapsed after receiving multidrug therapy, including Vindesine.

C43H55N5O7

753.93

753.41

53643-48-4

Vindesine sulfate;59917-39-4

40839

Crystal from ethanol-methanol

1.4±0.1 g/cm3

230-232ºC

1.708

2.94

5

10

7

55

1570

9

CC[C@]1(O)C[C@@H]2C[C@](C3=C(C4=CC=CC=C4N3)CCN(C1)C2)(C(OC)=O)C5=C(OC)C=C6C([C@]78CCN9CC=C[C@]([C@@H]79)([C@@H](O)[C@@](C(N)=O)(O)[C@@H]8N6C)CC)=C5

HHJUWIANJFBDHT-KOTLKJBCSA-N

InChI=1S/C43H55N5O7/c1-6-39(52)21-25-22-42(38(51)55-5,33-27(13-17-47(23-25)24-39)26-11-8-9-12-30(26)45-33)29-19-28-31(20-32(29)54-4)46(3)35-41(28)15-18-48-16-10-14-40(7-2,34(41)48)36(49)43(35,53)37(44)50/h8-12,14,19-20,25,34-36,45,49,52-53H,6-7,13,15-18,21-24H2,1-5H3,(H2,44,50)/t25-,34+,35-,36-,39+,40-,41-,42+,43+/m1/s1

methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-carbamoyl-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)