Apatinib Mesylate
(Synonyms: 阿帕替尼) 目录号 : GC14292
A selective VEGFR2 inhibitor
Cas No.:811803-05-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Primary cells established by s.c. tumors |
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Preparation Method |
Apatinib was dissolved in DMSO to yield a 151 mM stock solution, which was then diluted to the specified concentration in subsequent experiment by using DMEM. |
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Reaction Conditions |
Cells were treated with different concentrations of apatinib (0, 12.5, 25, 50 and 100 mM) for 24, 48, and 72 h, respectively. |
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Applications |
This could be used to test the ability of apatinib on the inhibitions of MPM Cells’ viability and proliferation. These gradient concentrations of apatinib inhibited cells proliferation; the inhibitory effect of apatinib on MPM cells showed the dose-dependent and time-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Specific pathogen free BALB/c nu/nu mice, 4–5 weeks old, 16–18 g |
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Preparation Method |
MPM surgical specimens was made to establish patient-derived xenograft (PDX) models in nude mice. Eighteen nude mice were randomly divided into three groups: blank control, solvent control and apatinib groups. Blank control group received no intervention, solvent control group was administrated with 24 mg/g/day 0.5% CMC, and treatment group was treated with 100 mg/g/day apatinib delivered by intra-gastric gavage. The treatment process lasted for 2 weeks. |
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Dosage form |
100 mg/g/day; apatinib was diluted in 0.5% Carboxymethyl Cellulose-Na solution |
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Applications |
This could be used to test the efficacy and toxicity of apatinib on MPM PDX Model. Results indicated that apatinib did not affect the weight of nude mice, and no adverse effects were observed during the construction of mice models. The positive rate of Ki-67 in apatinib group is significantly lower than that in control group |
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References: [1]. Yang ZR, et al. Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo. Front Oncol. 2020 Dec 7;10:585079. |
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Apatinib blocks the downstream signal transduction of VEGF pathway to inhibit neovascularization. Apatinib has showed antitumor effects on many kinds of tumors, such as sarcoma, breast cancer, ovarian cancer, and acute lymphoblastic leukemia (ALL). Moreover, a recent case report provided supporting information for apatinib to treat epithelioid malignant plural mesothelioma.[1]
In vitro experiment indicated that apatinib inhibited cells proliferation in a dose-dependent and time-dependent manner. The IC50 values of apatinib in MPM cells for treatment time 24 h, 48 h, 72 h were 46.34 μM, 45.14 μM, 28.73 μM.[3]
In vivo experiments demonstrated that apatinib inhibits tumor growth and metastasis. The ePCI score of blank control, solvent control and apatinib groups were 9.8 ± 0.9, 10.3 ± 0.9, and 7.3 ± 1.6, respectively. The differences were statistically significant (P = 0.003 for all; P = 0.008, blank control vs. apatinib group; P = 0.001, solvent control vs. apatinib group; P = 0.394, blank control vs. solvent control). The positive rate of Ki-67 in apatinib group was (17.0 ± 8.0)%, which is significantly lower than that in control group (48.1 ±11.5) % (P = 0.000); the positive rate of VEGFR-2 in apatinib group was slightly lower than that in control group, indicating no statistical significance.[1]
References:
[1]. Yang ZR, et al. Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo. Front Oncol. 2020 Dec 7;10:585079.
阿帕替尼阻断 VEGF 通路的下游信号转导，从而抑制新生血管形成。阿帕替尼对肉瘤、乳腺癌、卵巢癌、急性淋巴细胞白血病（ALL）等多种肿瘤均显示出抗肿瘤作用。此外，最近的病例报告为阿帕替尼治疗上皮样恶性多发性间皮瘤提供了支持信息。[1]
体外实验表明，阿帕替尼以剂量依赖性和时间依赖性方式抑制细胞增殖。阿帕替尼作用于MPM细胞24 h、48 h、72 h的IC50值分别为46.34 μM、45.14 μM、28.73 μM。[3]
体内实验表明，阿帕替尼可抑制肿瘤生长和转移。空白对照、溶剂对照和阿帕替尼组的ePCI评分分别为9.8±0.9、10.3±0.9和7.3±1.6。差异具有统计学意义（所有 P = 0.003；P = 0.008，空白对照与阿帕替尼组；P = 0.001，溶剂对照与阿帕替尼组；P = 0.394，空白对照与溶剂对照）。阿帕替尼组Ki-67阳性率为（17.0±8.0）%，显着低于对照组的（48.1±11.5）%（P=0.000）；阿帕替尼组VEGFR-2阳性率略低于对照组，无统计学意义。[1]
| Cas No. | 811803-05-1 | SDF | |
| 别名 | 阿帕替尼 | ||
| 化学名 | N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;methanesulfonic acid | ||
| Canonical SMILES | CS(=O)(=O)O.C1CCC(C1)(C#N)C2=CC=C(C=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4 | ||
| 分子式 | C25H27N5O4S | 分子量 | 493.58 |
| 溶解度 | ≥ 49.4mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.026 mL | 10.1301 mL | 20.2601 mL |
| 5 mM | 0.4052 mL | 2.026 mL | 4.052 mL |
| 10 mM | 0.2026 mL | 1.013 mL | 2.026 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Apatinib mesylate tablet in the treatment of advanced malignant melanoma
Onco Targets Ther.2018 Aug 31;11:5333-5338.PMID:30214239DOI: 10.2147/OTT.S175507.
Background: Observing and studying clinical efficacy and safety of apatinib mesylate tablet in the treatment of advanced malignant melanoma (MM). Methods: Retrospectively analyzing the clinical data of 22 patients with metastatic MM who had failed conventional chemotherapy from June 2016 to January 2018. All patients took 500 mg of apatinib mesylate tablets per day. The efficacy should be evaluated according to RECIST 1.1 criteria. Adverse events (AEs) should be graded according to NCI-CTCAE 4.0. Results: There were two cases of partial remission (PR), 11 of stable disease (SD) and nine of progressive disease (PD) in the 22 patients with advanced MM, where the objective remission rate (ORR) was 9.1% and the disease control rate (DCR) was 59.1%. The median progression-free survival (PFS) was 7.5 months, and the 6-month progression-free survival rate (PFR) was 54.7%. Six patients died and the overall survival (OS) was not reached. AEs were controllable and all were in Grade 1-3. Conclusion: Apatinib mesylate tablets have a certain curative effect on patients with malignant melanomas of Stage IV who failed conventional chemotherapy. Apatinib mesylate tablets at a daily dose of 500 mg are well tolerated by most patients.
Effects of Apatinib Mesylate Monotherapy on the Incidence of Adverse Reactions and Immune Function in Patients with Breast Cancer after Radical Mastectomy
Evid Based Complement Alternat Med.2022 Aug 10;2022:4022282.PMID:35990841DOI: 10.1155/2022/4022282.
Objective: To assess the effects of monotherapy with apatinib mesylate on the incidence of adverse events and immune function in breast cancer patients after a radical mastectomy. Methods: Between December 2018 and August 2020, 90 patients with breast cancer scheduled for a radical mastectomy in People's Liberation Army Navy 971 Hospital were randomly recruited and assigned at a ratio of 1 : 1 to receive either conventional treatment (conventional group) or apatinib mesylate after radical mastectomy (study group). The primary endpoint was disease control rate (DCR), and the secondary endpoints were adverse events and the immune function of the patients. Results: Monotherapy with apatinib mesylate was associated with a higher DCR (86.67%) versus conventional postoperative treatment (42.23%). All patients in the study group had documented adverse events, including 2 (4.45%) cases of headache, 3 (6.67%) cases of dizziness, 9 (20.00%) cases of hypertension, 6 (13.34%) cases of hand-foot syndrome, 3 (6.67%) cases of thrombocytopenia, 1 (2.23%) case of tinnitus, 7 (15.56%) cases of fatigue, 2 (4.45%) cases of anemia, 2 (4.45%) cases of oral pain, and 10 (22.23%) cases of leukopenia. There were 23 cases of intermittent discontinuation due to adverse events during treatment, 15 cases of dose reduction, and 3 cases of discontinuation due to adverse events. The difference in preoperative and postoperative T-cell subsets and natural killer (NK) cells between the two groups did not come up to the statistical standard (P > 0.05). Monotherapy with apatinib mesylate resulted in significantly lower levels of CD4+, CD4+/CD8+, and NK cells and higher CD8+ levels versus conventional treatment at 1 week and 4 weeks postoperatively (P < 0.05). Conclusion: Apatinib mesylate monotherapy after radical mastectomy yields a high DCR, a lower incidence of adverse events, and improved immune recovery. Clinical trials are, however, required prior to clinical promotion.
Effect of different doses of apatinib mesylate combined with chemotherapy on advanced oral cancer
Am J Transl Res.2021 Dec 15;13(12):13902-13908.PMID:35035731
Objective: To investigate the therapeutic effect and safety of different doses of apatinib mesylate combined with chemotherapy in the treatment of advanced oral cancer. Methods: Totally 100 patients with advanced oral cancer admitted to our hospital from January 2019 to July 2020 were retrospectively analyzed and divided into a control group (500 mg apatinib mesylate combined with chemotherapy) and an experimental group (250 mg apatinib mesylate combined with chemotherapy). The two groups were compared in terms of the incidence of adverse reactions, treatment effective rate, disease control rate, objective response rate, Karnofsky performance status (KPS) score (quality of life), score of the mental status scale in non-psychiatric settings (MSSNS), survival rates and vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) after treatment. In addition, logistic regression was used to analyze the influencing factors for KPS<85 after oral cancer treatment. Results: The treatment effective rate, disease control rate, objective response rate, KPS score (quality of life), survival rates in the experimental group were all significantly improved compared to those in the control group (all P<0.05), and the incidence of adverse reactions, MSSNS score, and the levels of VEGF and VEGFR-2 after treatment in the experimental group were significantly lower than those in the control group (all P<0.05). Furthermore, a history of smoking, a history of drinking, a tooth brushing index <3, the frequency of teeth cleansing ≤1 time per year, a history of oral diseases >3 times, and poor nutritional status were independent risk factors for KPS<85 after oral cancer treatment. Conclusion: Apatinib mesylate (250 mg) combined with chemotherapy can reach optimal efficacy with highest safety but least adverse effects for patients with advanced oral cancer.
Apatinib for the treatment of gastric cancer
Expert Opin Pharmacother.2015 Jan;16(1):117-22.PMID:25420417DOI: 10.1517/14656566.2015.981526.
Introduction: Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients. Areas covered: The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo. Expert opinion: Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.
Combined use of apatinib mesylate and vinorelbine versus vinorelbine alone in recurrent or metastatic triple-negative breast cancer: study protocol for a randomized controlled clinical trial
Trials.2020 May 24;21(1):420.PMID:32448335DOI: 10.1186/s13063-020-04342-x.
Background: The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; the future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate, a novel, small anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib mesylate also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby strongly inhibiting tumor angiogenesis and exerting an anti-tumor effect. However, there have been no reports of a randomized controlled clinical trial of apatinib combined with vinorelbine for the treatment of triple-negative breast cancer (TNBC). We will compare the therapeutic effect of vinorelbine alone or in combination with apatinib mesylate, in patients with recurrent or metastatic TNBC in North China who have received at least two drug treatments, including anthracyclines and taxanes. Methods/analysis: This study is a triple-blind, randomized, placebo-controlled, parallel-group clinical trial. We plan to include 238 female patients with locally recurrent or metastatic TNBC, admitted to the Liaoning Cancer Hospital & Institute, Northeast China. All enrolled patients will be randomized to oral vinorelbine alone (40 mg, thrice a week (Mondays, Wednesdays, and Fridays) in each 3-week cycle), or in combination with oral apatinib mesylate (500 mg, once daily in each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks and every 9 weeks thereafter. The primary outcome is progression-free survival and secondary outcomes include overall survival, disease control rate, objective response rate, and incidence of adverse events at grades 3 and 4, as defined by the National Cancer Institute Common Toxicity Criteria Version 4.0. Outcome measures will be evaluated at baseline (< 2 weeks before starting treatment), every 6 weeks during treatment, and at 4 weeks and every 3 months after treatment discontinuation. Discussion: Based on the data from this trial, we hope to identify a treatment plan that is suitable for female patients with TNBC, who have been treated with anthracyclines and taxanes, in Northeast China. Trial registration: ClinicalTrials.gov: NCT03932526. Registered on 30 April 2019.