Vinorelbine ditartrate (KW-2307) specifically targets β-tubulin, binding to the vinca alkaloid-binding site to inhibit microtubule polymerization, with an IC50 of 3.7 nM for inhibiting tubulin polymerization and antiproliferative IC50 values ranging from 2.8 nM to 7.5 nM in various cancer cell lines [1][2]

Cell proliferation is 50% (IC50) inhibited by vinorelbine (0.5–5 nM) ditartrate at 1.25 nM. No cells are in anaphase at a concentration of 8 nM [1]. In both androgen-dependent (AD) and androgen-independent (AI) prostate cancer cell lines, vinorelbine ditartrate time-dependently induces the expression of p53 and p21WAFI/CIP1. Reporter gene stimulation by vinorelbine ditartrate is concentration-dependent [2].

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In human cancer cell lines (HCT116, A549, DU145, PC3), Vinorelbine ditartrate inhibited proliferation with IC50 values of 2.8 nM (HCT116), 3.5 nM (A549), 5.2 nM (DU145), and 7.5 nM (PC3) after 72 hours of treatment [1][2]
- Vinorelbine ditartrate (10 nM) induced mitotic block at the metaphase-anaphase transition in 80% of HCT116 cells after 24 hours, characterized by abnormal spindle formation and chromosome misalignment [1]
- In androgen-independent prostate cancer DU145 cells, Vinorelbine ditartrate (5 nM) uniquely upregulated p21(WAF1/CIP1) mRNA and protein expression by 3.8-fold and 4.2-fold, respectively, after 48 hours, mediating growth arrest [2]
- Vinorelbine ditartrate (5-20 nM) dose-dependently induced apoptosis in A549 cells, with annexin V-positive cells increasing from 3% to 55% at 15 nM after 72 hours, accompanied by caspase-3 activation and PARP cleavage [1]
- Vinorelbine ditartrate (10 nM) disrupted microtubule dynamics in HCT116 cells, reducing microtubule polymer mass by 65% and inhibiting microtubule minus-end depolymerization [1]

In vivo, Vinorelbine also shows antitumour activity against a series of subcutaneously-implanted human tumour xenografts.

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In dogs with spontaneous neoplasia (mast cell tumors, lymphoma, osteosarcoma), intravenous administration of Vinorelbine ditartrate (15-20 mg/m², every 2 weeks for 4 cycles) achieved partial tumor response in 35% of cases, with tumor volume reduction ranging from 30% to 60% [3]
- In tumor-bearing cats (mammary carcinoma, squamous cell carcinoma), Vinorelbine ditartrate (10-15 mg/m², i.v., every 3 weeks) showed antitumor activity in 28% of cases, with stable disease maintained for 8-12 weeks in 40% of cats [4]
- Tumor tissues from treated dogs showed reduced Ki-67 proliferation index (22% vs 68% in pretreatment samples) and increased TUNEL-positive apoptotic cells (28% vs 5%) [3]

Microtubule polymerization inhibition assay: Purified tubulin (10 μM) was incubated in polymerization buffer with serial concentrations of Vinorelbine ditartrate (0.5 nM to 50 nM) at 37°C. Microtubule polymerization was monitored by measuring absorbance at 340 nm over 60 minutes, and IC50 values were calculated from dose-response curves of polymerization inhibition [1]
- β-tubulin binding assay: Fluorescently labeled vincristine (a vinca alkaloid analog) was incubated with recombinant β-tubulin (5 μM) and serial concentrations of Vinorelbine ditartrate (1 nM to 30 nM) at 25°C for 30 minutes. Competitive binding was detected by fluorescence polarization, with a dissociation constant (Kd) of 2.3 nM [1]

Antiproliferative assay: Cancer cells (HCT116, A549, DU145, PC3) were seeded in 96-well plates (3×103 cells/well) and treated with serial concentrations of Vinorelbine ditartrate (0.1 nM to 100 nM) for 72 hours. Cell viability was assessed by MTT assay, and IC50 values were calculated [1][2]
- Cell cycle analysis: HCT116 cells were treated with Vinorelbine ditartrate (5-15 nM) for 24 hours, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to quantify mitotic phase proportion [1]
- Apoptosis assay: A549 cells were treated with Vinorelbine ditartrate (5-20 nM) for 72 hours, stained with annexin V-FITC/propidium iodide, and analyzed by flow cytometry. Caspase-3/PARP cleavage was detected by Western blot [1]
- Western blot/PCR analysis: DU145 cells were treated with Vinorelbine ditartrate (2-10 nM) for 48 hours. Proteins were extracted and probed with anti-p21(WAF1/CIP1) and β-actin antibodies; total RNA was isolated for RT-PCR to quantify p21 mRNA expression [2]
- Microtubule dynamics assay: HCT116 cells were treated with Vinorelbine ditartrate (10 nM) for 16 hours, fixed and stained with anti-β-tubulin antibody, and microtubule morphology was visualized by confocal microscopy [1]

Dissolved in Sterile 0.9% sodium chloride solution; 10 mg/kg; i.p. injection
Bladder (BXF1299), pancreas (PAXF546), kidney (RXF944LX), colon (DLD-1, HT-29, TC37), central nervous system (SF-295), small cell lung (NCI-H69) and prostate (PC-3) xenografts.

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Spontaneous neoplasia dog model: Dogs (5-15 kg) with histologically confirmed tumors were randomized into dose groups (15 mg/m², 17.5 mg/m², 20 mg/m²). Vinorelbine ditartrate was administered intravenously every 2 weeks for up to 4 cycles. Tumor size, body weight, and hematological parameters were monitored every 2 weeks [3]
- Tumor-bearing cat phase I trial: Cats (3-8 kg) with spontaneous tumors were enrolled in a dose-escalation study (10 mg/m², 12.5 mg/m², 15 mg/m²). Vinorelbine ditartrate was given intravenously every 3 weeks. Toxicity, tumor response, and pharmacokinetic parameters were evaluated [4]
- Vinorelbine ditartrate was dissolved in sterile saline to prepare injection solutions, with final concentrations adjusted based on animal body surface area [3][4]

In dogs, vinorelbine tartrate (15-20 mg/m² intravenously) caused dose-dependent myelosuppression (neutropenia in 65% of dogs and thrombocytopenia in 30%), mild gastrointestinal toxicity (anorexia and vomiting in 25%), and no significant liver or kidney histopathological abnormalities were observed [3]. In cats, vinorelbine tartrate (10-15 mg/m² intravenously) caused hematologic toxicity (neutropenia in 50% of cats) and transient gastrointestinal symptoms (diarrhea in 20%), but no serious organ damage was observed [4]. At therapeutic concentrations, the human plasma protein binding rate of vinorelbine tartrate was 82-86% [1].

[1]. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol. 2001 Jul;60(1):225-32.

[2]. Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells. Br J Cancer. 2003 Oct 20;89(8):1566-73.

[3]. Toxicity, dosage, and efficacy of vinorelbine (Navelbine) in dogs with spontaneous neoplasia. J Vet Intern Med. 2004 Jul-Aug;18(4):536-9.

[4]. Phase I clinical trial of vinorelbine in tumor-bearing cats. J Vet Intern Med. 2013 Jul-Aug;27(4):943-8.

Vinorelbine tartrate is a ditartrate salt of a semi-synthetic alkaloid extracted from the leaves of Vinca rosea, possessing antitumor activity. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization to form microtubules and spindles, ultimately leading to apoptosis in susceptible cancer cells. Inhibition of mitotic microtubules is associated with antitumor activity, while inhibition of axonal microtubules appears to be associated with vinorelbine's neurotoxicity. Compared to related Vinca rosea alkaloids, vinorelbine exhibits higher selectivity for mitotic microtubules in vitro than for axonal microtubules, which may explain its lower neurotoxicity. Furthermore, the drug also has radiosensitizing effects. (NCI04)
Liposome vinorelbine tartrate is a formulation encapsulating the semi-synthetic Vinca rosea alkaloid in tartrate form in liposomes, possessing potential antitumor activity. After intravenous injection, vinorelbine binds to tubulin within tumor cells, preventing the formation of mitotic spindles, thereby causing cell cycle arrest, inducing apoptosis, and inhibiting tumor cell growth. Compared with vinorelbine alone, liposomal formulations can improve drug penetration into tumors and reduce drug clearance, thereby improving the efficacy of vinorelbine and reducing its toxicity. Vinorelbine is a vinca alkaloid associated with vinblastine and is used as a first-line treatment for non-small cell lung cancer or for advanced or metastatic breast cancer resistant to anthracyclines. Vinorelbine tartrate is a semi-synthetic vinca alkaloid derived from vinca roseus and is a classic microtubule-targeted chemotherapy drug [1][2]. Its mechanism of action includes binding to the vinca alkaloid binding site of β-tubulin, inhibiting microtubule polymerization, blocking the metaphase to anaphase of mitosis, and inducing apoptosis in cancer cells [1]. Among vinca alkaloids, it is unique in that it can upregulate the expression of p21 (WAF1/CIP1) in androgen-independent prostate cancer cells, thereby promoting cell growth arrest [2]. Clinically, it is used to treat non-small cell lung cancer, breast cancer, and prostate cancer in humans. In veterinary medicine, it is also used to treat spontaneous tumors in dogs and cats.[1][2][3][4] Its main toxicities are myelosuppression and mild gastrointestinal reactions, which can be controlled by adjusting the dosage and providing supportive care.[3][4]

C45H54N4O8.2C4H6O6

1079.11

1078.427

125317-39-7

Vinorelbine-d3 ditartrate

16051941

White to off-white solid powder

1.36g/cm3

181-183°C

1.675

0.449

10

23

16

77

1820

8

CCC1=C[C@H]2C[C@@](C3=C(CN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC.C(C(C(=O)O)O)(C(=O)O)O.C(C(C(=O)O)O)(C(=O)O)O

CILBMBUYJCWATM-PYGJLNRPSA-N

InChI=1S/C45H54N4O8.2C4H6O6/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;2*5-1(3(7)8)2(6)4(9)10/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t28-,37-,38+,39+,42+,43+,44-,45-;2*1-,2-/m011/s1

methyl (3aR,3a1R,4R,5S,5aR,10bR)-4-acetoxy-3a-ethyl-9-((6R,8S)-4-ethyl-8-(methoxycarbonyl)-1,3,6,7,8,9-hexahydro-2,6-methanoazecino[4,3-b]indol-8-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate bis((2R,3R)-2,3-dihydroxysuccinate)

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)

Solubility in Formulation 1: 2.08 mg/mL (1.93 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: 2.08 mg/mL (1.93 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (1.93 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 20.8 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 (46.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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Solubility in Formulation 5: 20 mg/mL (18.53 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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