nAChR (IC50 = 8.9 μM)
Vinblastine targets tubulin, the protein subunit of microtubules. It binds to tubulin and inhibits normal microtubule assembly, inducing aberrant tubulin polymerization. This disrupts the formation of the mitotic spindle, leading to cell cycle arrest at the G2/M phase and subsequent apoptosis. Vinblastine also suppresses neuronal nicotinic acetylcholine receptors (nAChRs) with an IC50 of 8.9 μM.

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].
In vitro, vinblastine inhibits microtubule assembly and induces aberrant tubulin polymerization. It induces cell cycle arrest at G2/M phase and apoptosis in cancer cell lines. It shows cytotoxic activity against various cancer cell lines. The compound's IC50 for nAChR inhibition is 8.9 μM. These activities confirm its mechanism as a microtubule-disrupting agent.

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].
In vivo, vinblastine sulfate is therapeutically used as an antineoplastic agent. It is used to treat Hodgkin's disease, lymphosarcoma, reticulum cell sarcoma, neuroblastoma, choriocarcinoma, and carcinomas of the breast, lung, oral cavity, testis, and bladder. It is also used for acute and chronic leukemia, histiocytosis, and mycosis fungoides. The compound's antitumor activity is attributed to its antimitotic effects.

In vitro tubulin binding assays for vinblastine measure binding to tubulin using radiolabeled vinblastine or competition with other tubulin-binding agents. Microtubule assembly is assessed spectrophotometrically by measuring turbidity at 350 nm. Various concentrations of vinblastine are added. Inhibition of assembly or induction of aberrant polymerization is quantified. IC50 values are calculated from dose-response curves.

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.
Cellular assays for vinblastine use various cancer cell lines. Cells are treated with various concentrations of vinblastine. Cell cycle analysis is performed by flow cytometry to assess G2/M arrest. Apoptosis is assessed by caspase-3/7 activity or Annexin V staining. Cell viability is measured using MTT or ATP-lite assays. These assays confirm the compound's cytotoxic and antimitotic activity.

In vivo animal studies for vinblastine utilize tumor xenograft models in mice. The compound is administered intravenously or intraperitoneally. Tumor volume is measured over time. Survival is monitored. Efficacy is compared to vehicle and reference chemotherapeutic agents. Pharmacokinetic sampling is performed to correlate exposure with efficacy. Toxicity and tolerability are monitored.

Vinblastine sulfate has molecular weight of approximately 909.06 g/mol and molecular formula C46H60N4O13S. It is a white to slightly yellow crystalline powder. It is soluble in water. It is typically stored at room temperature. Pharmacokinetic properties include extensive tissue binding, hepatic metabolism, and biliary excretion. The compound has a long terminal half-life.

Effects During Pregnancy and Lactation
◉ Overview of Lactational Use
Most data suggest that mothers should not breastfeed while receiving anti-tumor drug treatment. Due to the long half-life of vinblastine, resuming breastfeeding after vinblastine treatment may not be practical. Chemotherapy may adversely affect the normal microbiota and chemical composition of breast milk. Women receiving chemotherapy during pregnancy are more likely to experience breastfeeding difficulties. ◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk
A woman diagnosed with Hodgkin's lymphoma in mid-pregnancy received three cycles of chemotherapy in late pregnancy and resumed chemotherapy four weeks postpartum. Breast milk samples were collected 15 to 30 minutes before and after chemotherapy within 16 weeks after resuming chemotherapy. The regimen consisted of doxorubicin 40 mg, bleomycin 16 units, vinblastine 9.6 mg, and dacarbazine 600 mg, administered every two weeks over two hours. Researchers compared the microbiome and metabolome of this patient's breast milk with those of eight healthy women who did not receive chemotherapy. The results showed a significant difference between the patient's and healthy women's breast milk microbiome, with increased numbers of Acinetobacter, Xanthomonas, and Stenotrophomonas maltophilia, while decreasing numbers of Bifidobacterium and Eubacterium. Furthermore, several chemical components in the patient's breast milk also differed significantly, with significantly lower levels of DHA and inositol. A telephone follow-up study investigated 74 women who received chemotherapy for cancer in the second or third trimester at the same center to determine their postpartum breastfeeding success rate. Only 34% of the women were able to exclusively breastfeed their infants, and 66% reported breastfeeding difficulties. In contrast, among the 22 mothers diagnosed with cancer during pregnancy but who did not receive chemotherapy, the breastfeeding success rate was as high as 91%. Other statistically significant correlations included: 1. Mothers with breastfeeding difficulties received an average of 5.5 cycles of chemotherapy, while mothers without breastfeeding difficulties received an average of 3.8 cycles; 2. Mothers with breastfeeding difficulties received their first chemotherapy treatment an average of 3.4 weeks earlier than mothers without breastfeeding difficulties. Of the six women treated with vincristine-containing regimens, five had breastfeeding difficulties.
Vinblastine sulfate has significant toxicity, which limits its clinical use. Common adverse effects include myelosuppression (neutropenia, thrombocytopenia), nausea, vomiting, alopecia, neurotoxicity (peripheral neuropathy), and local tissue irritation at the injection site. Cardiotoxicity and hepatotoxicity may also occur. Dose-limiting toxicity is myelosuppression. The compound should be handled with caution.

[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.

According to state or federal labeling requirements, vinblastine sulfate may cause developmental toxicity. Vincristine sulfate is an anticancer drug. It is a white to slightly yellow crystalline powder. (NTP, 1992) Vincristine sulfate is the sulfate of vinblastine, a natural alkaloid isolated from the periwinkle (Catharanthus roseus) with antitumor properties. Vinblastine disrupts the formation and function of microtubules during mitosis and interferes with glutamate metabolism. (NCI04) An antitumor alkaloid isolated from periwinkle. (Merck, 11th edition) See also: Vincristine (with active fraction).
Vinblastine sulfate is an antimicrotubule drug derived from Catharanthus roseus. It is used as an antineoplastic agent for various cancers. It induces G2/M arrest by inhibiting mitotic spindle formation. It also suppresses nAChRs with an IC50 of 8.9 μM. It is a clinically approved drug for cancer treatment.

C46H60N4O13S

909.05

908.387

C, 60.78; H, 6.65; N, 6.16; O, 22.88; S, 3.53

143-67-9

143-67-9 (sulfate);865-21-4 (free);

5388983

White to slight yellow solid powder

1.37 g/cm3

543 to 545 °F (NTP, 1992)

Originated from plants: Apocynaceae Catharanthus roseus (L.) G. Don

4.359

5

16

10

64

1780

9

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]

KDQAABAKXDWYSZ-JKDPCDLQSA-N

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

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

Vincaleucoblastine; VLB; Velsar; Velban

2934.99.9001

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.

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

DMSO: ~100 mg/mL (~110 mM)
Water: ~50 mg/mL (~55 mM)

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.

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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.

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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.

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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.

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