Metabolism / Metabolites
Hepatic
Hepatic
Half Life: 24 hours.

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Biological Half-Life
24 hours.

Toxicity Summary
Vindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.

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Protein Binding
65-75%

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Toxicity Data
LD50: 4 mg/kg (Mouse)

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Interactions
Leukopenic and/or thrombocytopenic effects of vindesine may be increased with concurrent or recent therapy if these medications /blood dyscrasia causing medications/ cause the same effects; dosage adjustment of vindesine, if necessary, should be based on blood counts.
Additive bone marrow depression, including severe dermatitis and/or mucositis, may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively.
Acute shortness of breath and severe bronchospasm have frequently been reported with combination therapy including vinca alkaloids; the reaction may occur within minutes or several hours after the vinca alkaloid is injected.
Neurologic toxicity may occur early in treatment and may be more severe if used concomitantly with other drugs having a neurotoxic potential.
For more Interactions (Complete) data for VINDESINE (7 total), please visit the HSDB record page.

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

Vindesine is a vinca alkaloid, a methyl ester, an organic heterotetracyclic compound, an organic heteropentacyclic compound, a tertiary alcohol, a tertiary amino compound and a primary carboxamide. It has a role as an antineoplastic agent. It is functionally related to a vincaleukoblastine.
Vinblastine derivative with antineoplastic activity against cancer. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (antineoplastic combined chemotherapy protocols).
Vindesine is a synthetic derivative of vinblastine, a naturally occurring vinca alkaloid. Vindesine binds to and stabilizes tubulin, thereby interrupting tubulin polymerization and preventing the formation of the mitotic spindle and cell division; treated cells are unable to undergo mitosis and are arrested in metaphase. This agent also disrupts macromolecular synthesis. (NCI04)
Vindesine is only found in individuals that have used or taken this drug. It is a vinblastine derivative with antineoplastic activity against cancer. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (antineoplastic combined chemotherapy protocols). Vindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.
Vinblastine derivative with antineoplastic activity against CANCER. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS).

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Drug Indication
For the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia and acute panmyelosis

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Mechanism of Action
Vindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.
Vindesine causes the arrest of cells in metaphase mitosis. It is three times more potent than vincristine and nearly 10 times more potent than vinblastine in causing mitotic arrest in in vitro studies at doses designed to arrest from 10 to 15% of the cells in mitosis.Vindesine and vincristine are approximately equipotent at dose levels that arrest 40 to 50% of the cells in mitosis. Unlike vinblastine, vindesine produces very few postmetaphase cells.Vindesine has demonstrated activity in patients who have relapsed while receiving multiple-agent treatment that included vincristine. Toxic doses of vindesine given to male and female rats have not affected fertility.

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Therapeutic Uses
Vindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine. /Included in US product labeling/
Vindesine is indicated for the treatment of non-oat cell lung cancer. /Included in US product labeling/

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Drug Warnings
Benefit-to-risk ratio must be considered before using vindesine in pregnant women. It usually is recommended that use of antineoplastics, especially combination chemotherapy, be avoided during pregnancy whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered. Other hazards to the fetus include adverse reactions seen in adults.
Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of vindesine in children.
It is important to strictly adhere to the recommended dosage schedule. The use of small amounts of vindesine daily for long periods for the treatment of children with acute lymphocytic leukemia is not advised, even though the resulting weekly dosage may be similar to the recommended dosage. Little or no therapeutic benefit has been demonstrated when such regimens are used, and the incidence of adverse reactions is increased
The bone marrow depressant effects of vindesine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

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Pharmacodynamics
Vindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine and non-oat cell lung cancer. Vindesine causes the arrest of cells in metaphase mitosis. It is three times more potent than vincristine and nearly 10 times more potent than vinblastine in causing mitotic arrest in in vitro studies at doses designed to arrest from 10 to 15% of the cells in mitosis. Vindesine and vincristine are approximately equipotent at dose levels that arrest 40 to 50% of the cells in mitosis. Unlike vinblastine, vindesine produces very few postmetaphase cells. Vindesine has demonstrated activity in patients who have relapsed while receiving multiple-agent treatment that included vincristine.

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.)