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Vinorelbine ditartrate (KW-2307; KW2307; Navelbine, Biovelbin, Eunades; Nor-5'-anhydrovinblastine), the ditartrate salt of vinorelbine which is an antimitotic agent, is a tubulin inhibitor and microtubule stablizer approved for cancer treatment. It is a semisynthetic vinca alkaloid derived from the leaves of the periwinkle plant (Vinca rosea) and has been used extensively for the treatment for various cancers such as breast cancer and non-small cell lung cancer.
Physicochemical Properties
| Molecular Formula | C45H54N4O8.2C4H6O6 | |
| Molecular Weight | 1079.11 | |
| Exact Mass | 1078.427 | |
| CAS # | 125317-39-7 | |
| Related CAS # | Vinorelbine-d3 ditartrate | |
| PubChem CID | 16051941 | |
| Appearance | White to off-white solid powder | |
| Density | 1.36g/cm3 | |
| Melting Point | 181-183°C | |
| Index of Refraction | 1.675 | |
| LogP | 0.449 | |
| Hydrogen Bond Donor Count | 10 | |
| Hydrogen Bond Acceptor Count | 23 | |
| Rotatable Bond Count | 16 | |
| Heavy Atom Count | 77 | |
| Complexity | 1820 | |
| Defined Atom Stereocenter Count | 8 | |
| SMILES | 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 |
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| InChi Key | CILBMBUYJCWATM-PYGJLNRPSA-N | |
| InChi Code | 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 | |
| Chemical Name | 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) | |
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| 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. |
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| 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
| ln Vitro | 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]. | ||
| ln Vivo |
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| Animal Protocol |
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| References |
[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. |
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| Additional Infomation |
Vinorelbine Tartrate is the ditartrate salt of a semisynthetic vinca alkaloid derived from the leaves of the periwinkle plant (Vinca rosea) with antineoplastic properties. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization into microtubules and spindle formation and resulting in apoptosis of susceptible cancer cells. Inhibition of mitotic microtubules correlates with antitumor activity, whereas inhibition of axonal microtubules seems to correlate with vinorelbine's neurotoxicity. Compared to related vinca alkaloids, vinorelbine is more selective against mitotic than axonal microtubules in vitro, which may account for its decreased neurotoxicity. This agent is also a radiation-sensitizing agent. (NCI04) Liposomal Vinorelbine Tartrate is a formulation of the tartrate salt form of vinorelbine, a semisynthetic vinca alkaloid, encapsulated within liposomes, with potential antineoplastic activity. Upon intravenous administration, vinorelbine binds to tubulin within tumor cells and prevents the formation of the mitotic spindle, resulting in cell cycle arrest, induction of apoptosis and an inhibition of tumor cell growth. Compared to the administration of vinorelbine alone, the liposomal formulation improves drug penetration into tumors and decreases drug clearance, thereby increasing vinorelbine's efficacy while lowering the toxicity profile. A vinca alkaloid related to VINBLASTINE that is used as a first-line treatment for NON-SMALL CELL LUNG CANCER, or for advanced or metastatic BREAST CANCER refractory to treatment with ANTHRACYCLINES. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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. 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. 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. 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9267 mL | 4.6334 mL | 9.2669 mL | |
| 5 mM | 0.1853 mL | 0.9267 mL | 1.8534 mL | |
| 10 mM | 0.0927 mL | 0.4633 mL | 0.9267 mL |