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]

1.25 nM 的二酒石酸长春瑞滨 (0.5–5 nM) 可抑制 50% (IC50) 细胞增殖。浓度为 8 nM 时没有细胞处于后期 [1]。在雄激素依赖性 (AD) 和雄激素非依赖性 (AI) 前列腺癌细胞系中，酒石酸长春瑞滨时间依赖性地诱导 p53 和 p21WAFI/CIP1 的表达。酒石酸长春瑞滨对报告基因的刺激具有浓度依赖性[2]。

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在人类癌细胞系（HCT116、A549、DU145、PC3）中，Vinorelbine ditartrate 抑制细胞增殖，72 小时处理后的 IC50 值分别为：HCT116（2.8 nM）、A549（3.5 nM）、DU145（5.2 nM）、PC3（7.5 nM）[1][2]
- 10 nM Vinorelbine ditartrate 处理 24 小时后，80% 的 HCT116 细胞在分裂中期 - 后期发生有丝分裂阻滞，表现为纺锤体形成异常和染色体排列紊乱 [1]
- 在雄激素非依赖性前列腺癌细胞 DU145 中，5 nM Vinorelbine ditartrate 独特地上调 p21(WAF1/CIP1) 的 mRNA 和蛋白表达，48 小时后分别增加 3.8 倍和 4.2 倍，介导细胞生长停滞 [2]
- Vinorelbine ditartrate（5-20 nM）剂量依赖性诱导 A549 细胞凋亡，15 nM 浓度处理 72 小时后，膜联蛋白 V 阳性细胞比例从 3% 升至 55%，伴随半胱天冬酶 -3 激活和 PARP 切割 [1]
- 10 nM Vinorelbine ditartrate 破坏 HCT116 细胞的微管动力学，使微管聚合质量减少 65%，并抑制微管负极解聚 [1]

在体内，长春瑞滨还对一系列皮下植入的人类肿瘤异种移植物显示出抗肿瘤活性。

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在患有自发性肿瘤（肥大细胞瘤、淋巴瘤、骨肉瘤）的犬中，静脉注射 Vinorelbine ditartrate（15-20 mg/m²，每 2 周一次，连续 4 个周期）使 35% 的病例达到部分肿瘤缓解，肿瘤体积缩小 30%-60% [3]
- 在肿瘤携带猫（乳腺癌、鳞状细胞癌）中，Vinorelbine ditartrate（10-15 mg/m²，静脉给药，每 3 周一次）在 28% 的病例中显示抗肿瘤活性，40% 的猫病情稳定维持 8-12 周 [4]
- 治疗后犬的肿瘤组织中，Ki-67 增殖指数降至 22%（治疗前样本为 68%），TUNEL 阳性凋亡细胞比例升至 28%（治疗前为 5%）[3]

微管聚合抑制实验：纯化微管蛋白（10 μM）与系列浓度的 Vinorelbine ditartrate（0.5 nM 至 50 nM）在聚合缓冲液中 37°C 孵育。60 分钟内通过检测 340 nm 吸光度监测微管聚合，从聚合抑制的剂量 - 反应曲线计算 IC50 值 [1]
- β- 微管蛋白结合实验：荧光标记的长春新碱（长春花生物碱类似物）与重组 β- 微管蛋白（5 μM）及系列浓度的 Vinorelbine ditartrate（1 nM 至 30 nM）25°C 孵育 30 分钟。荧光偏振法检测竞争性结合，Vinorelbine ditartrate 与 β- 微管蛋白的解离常数（Kd）为 2.3 nM [1]

抗增殖实验：癌细胞（HCT116、A549、DU145、PC3）接种于 96 孔板（3×103 个细胞 / 孔），用系列浓度的 Vinorelbine ditartrate（0.1 nM 至 100 nM）处理 72 小时。MTT 法评估细胞活力，计算 IC50 值 [1][2]
- 细胞周期分析：HCT116 细胞用 Vinorelbine ditartrate（5-15 nM）处理 24 小时，70% 乙醇固定，碘化丙啶染色，流式细胞术定量分裂期细胞比例 [1]
- 凋亡实验：A549 细胞用 Vinorelbine ditartrate（5-20 nM）处理 72 小时后，用膜联蛋白 V-FITC/碘化丙啶染色，流式细胞术分析。Western blot 检测半胱天冬酶 -3/PARP 切割 [1]
- Western blot/PCR 分析：DU145 细胞用 Vinorelbine ditartrate（2-10 nM）处理 48 小时。提取蛋白后与抗 p21(WAF1/CIP1) 及 β- 肌动蛋白抗体孵育；提取总 RNA 进行 RT-PCR，定量 p21 mRNA 表达 [2]
- 微管动力学实验：HCT116 细胞用 Vinorelbine ditartrate（10 nM）处理 16 小时，固定后用抗 β- 微管蛋白抗体染色，共聚焦显微镜观察微管形态 [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

363.99

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

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

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

配方 1 中的溶解度: 2.08 mg/mL (1.93 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.08 mg/mL (1.93 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (1.93 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 50 mg/mL (46.33 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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配方 5 中的溶解度: 20 mg/mL (18.53 mM) in Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。