 Chemical Structure.png)
Vinblastine sulfate (also known as NSC49842; Vincaleukoblastine), a natural alkaloid extracted from the plant Vinca rosea Linn, is an approved anticancer drug and a potent mitotic inhibitor that inhibits microtubule formation and suppresses nAChR activity with IC50 of 8.9 μM in a cell-free assay, it is used to treat certain kinds of cancer. Vinblastine binds to tubulin and prevents the formation of microtubules, which disrupts the assembly of mitotic spindles and stops tumor cells in the M phase of the cell cycle.
Physicochemical Properties
| Molecular Formula | C46H60N4O13S |
| Molecular Weight | 909.05 |
| Exact Mass | 908.387 |
| Elemental Analysis | C, 60.78; H, 6.65; N, 6.16; O, 22.88; S, 3.53 |
| CAS # | 143-67-9 |
| Related CAS # | 143-67-9 (sulfate);865-21-4 (free); |
| PubChem CID | 5388983 |
| Appearance | White to slight yellow solid powder |
| Density | 1.37 g/cm3 |
| Melting Point | 267 °C (dec.)(lit.) |
| LogP | 4.359 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 64 |
| Complexity | 1780 |
| Defined Atom Stereocenter Count | 9 |
| SMILES | S(=O)(=O)(O[H])O[H].O(C(C([H])([H])[H])=O)[C@@]1([H])[C@](C(=O)OC([H])([H])[H])([C@@]2([H])C3(C4=C([H])C([C@]5(C(=O)OC([H])([H])[H])C6=C(C7=C([H])C([H])=C([H])C([H])=C7N6[H])C([H])([H])C([H])([H])N6C([H])([H])[C@](C([H])([H])C([H])([H])[H])(C([H])([H])[C@]([H])(C6([H])[H])C5([H])[H])O[H])=C(C([H])=C4N2C([H])([H])[H])OC([H])([H])[H])C([H])([H])C([H])([H])N2C([H])([H])C([H])=C([H])[C@]1(C([H])([H])C([H])([H])[H])[C@]23[H])O[H] |
| InChi Key | KDQAABAKXDWYSZ-JKDPCDLQSA-N |
| InChi Code | InChI=1S/C46H58N4O9.H2O4S/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7;1-5(2,3)4/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3;(H2,1,2,3,4)/t28-,37+,38-,39-,42+,43-,44-,45+,46+;/m1./s1 |
| Chemical Name | methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;sulfuric acid |
| Synonyms | Vincaleucoblastine; VLB; Velsar; Velban |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | nAChR (IC50 = 8.9 μM) | ||
| ln Vitro | Vinblastine is a potent mitotic inhibitor (IC50 0.8 nM in HeLa cells), preventing cell death through apoptosis while not depolymerizing spindle microtubules[2]. Vinblastine causes p53 alteration and DNA fragmentation in NB4 cells. By inducing apoptosis and causing a Bax/Bcl-2 imbalance, vinblastine treatment has an antiproliferative effect. Treatment with vinblastine inhibits NFκB expression and decreases NFκB-DNA binding activity, all the while preserving JNK activation, which in turn triggers an apoptotic response via a caspase-dependent pathway[3]. Apoptosis inducing factor and cytochrome c release, cleavage of poly (ADP-ribose)-Polymerase, activation of caspase-9 and 3, and loss of mitochondrial membrane potential are all signs that vinblastine induces apoptosis[4]. | ||
| ln Vivo | Vinblastine is a popular anticancer medication that has unfavorable side effects. One effective way to lessen these side effects might be to conjugate it with carrier molecules[5]. | ||
| Cell Assay | Six-well treatment plates are prepared with 5 × 104 cells/mL in each well, suspended in 3 mL culture medium, and treated with vinblastine for three hours, followed by a growth period of twenty-one hours. | ||
| Animal Protocol |
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It is probably impractical to resume breastfeeding after vinblastine therapy because of the drug's long half-life. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk A woman diagnosed with Hodgkin's lymphoma during the second trimester of pregnancy received 3 rounds of chemotherapy during the third trimester of pregnancy and resumed chemotherapy 4 weeks postpartum. Milk samples were collected 15 to 30 minutes before and after chemotherapy for 16 weeks after restarting. The regimen consisted of doxorubicin 40 mg, bleomycin 16 units, vinblastine 9.6 mg and dacarbazine 600 mg, all given over a 2-hour period every 2 weeks. The microbial population and metabolic profile of her milk were compared to those of 8 healthy women who were not receiving chemotherapy. The breastmilk microbial population in the patient was markedly different from that of the healthy women, with increases in Acinetobacter sp., Xanthomonadacae and Stenotrophomonas sp. and decreases in Bifidobacterium sp. and Eubacterium sp. Marked differences were also found among numerous chemical components in the breastmilk of the treated woman, most notably DHA and inositol were decreased. A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 6 women who received a vincristine-containing regimen, 5 had breastfeeding difficulties. |
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| References |
[1]. Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6. [2]. Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets. J Mol Graph Model. 2014 Nov;54:1-9. [3]. JNK and NFκB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells. Cell Biochem Funct. 2015 Jun;33(4):211-9. [4]. Vinblastine-induced apoptosis of melanoma cells is mediated by Ras homologous A protein (Rho A) via mitochondrial and non-mitochondrial-dependent mechanisms. Apoptosis. 2013 Aug;18(8):980-97. [5]. Synthesis and in vitro antitumor effect of vinblastine derivative-oligoarginine conjugates. Bioconjug Chem. 2010 Nov 17;21(11):1948-55. |
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| Additional Infomation |
Vinblastine Sulfate can cause developmental toxicity according to state or federal government labeling requirements. Vinblastine sulfate appears as an anticancer drug. White to slightly yellow crystalline powder. (NTP, 1992) Vinblastine Sulfate is the sulfate salt of vinblastine, a natural alkaloid isolated from the plant Catharanthus roseus (Madagascar periwinkle) with antineoplastic properties. Vinblastine disrupts microtubule formation and function during mitosis and interferes with glutamic acid metabolism. (NCI04) Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.) See also: Vinblastine (has active moiety). |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~110 mM) Water: ~50 mg/mL (~55 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (2.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 50 mg/mL (55.00 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1000 mL | 5.5002 mL | 11.0005 mL | |
| 5 mM | 0.2200 mL | 1.1000 mL | 2.2001 mL | |
| 10 mM | 0.1100 mL | 0.5500 mL | 1.1000 mL |