Toceranib phosphate
(Synonyms: 托西尼布磷酸盐,SU11654 phosphate; PHA 291639E phosphate) 目录号 : GC37808
A multi-targeted receptor tyrosine kinase inhibitor
Cas No.:874819-74-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | The c-kit mutant canine C2 mastocytoma cell line, derived from a spontaneously occurring cutaneous mast cell tumors (MCTs), is used as the parental cell line. Cells are propagated in RPMI 1640 supplemented with 2 mM L-glutamine, 10% FBS, 100 g/mL Streptomycin, and 100 U/mL Penicillin in a 37°C incubator under a humidified atmosphere of 5% CO2. Toceranib-resistant C2 cells are selected by growing C2 cells in concentrations of Toceranib ranging from 0.02 uM to 0.3 uM and increasing in 0.025-0.05 uM increments. Three independent, Toceranib -resistant sublines are established over a period of 7 months[2]. |
Animal experiment: | Dogs[3]Fifteen client-owned dogs with advanced tumors are used. Dogs receive Toceranib at 2.75 mg/kg once every other day. After 2 weeks, oral cyclophosphamide (CYC) is added at 15 mg/m2 daily. Numbers of Treg and lymphocyte subsets are measured in blood by flow cytometry during the 8-week study period. Serum concentrations of IFN-γ are measured by ELISA. |
References: [1]. London CA, et al. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res. 2003 Jul;9(7):2755-68. | |
Toceranib is a small molecule, multi-targeted receptor tyrosine kinase inhibitor that is structurally related to sunitinib .1 It potently inhibits signaling through VEGFR, FGFR, PDGFR, and Kit.1 Moveover, toceranib blocks the autophosphorylation of both wild type and mutant forms of Kit in response to stem cell factor, resulting in cell death.1 It is active in vivo and is commonly used against solid tumors in dogs.2,3
1.Liao, A.T., Chien, M.B., Shenoy, N., et al.Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitorsBlood100(2)585-593(2002) 2.London, C., Mathie, T., Stingle, N., et al.Preliminary evidence for biologic activity of toceranib phosphate (Palladiar) in solid tumoursVet. Comp. Oncol.10(3)194-205(2012) 3.Ranieri, G., Gadaleta, C.D., Patruno, R., et al.A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapiesCrit. Rev. Oncol. Hematol.88187-197(2013)
| Cas No. | 874819-74-6 | SDF | |
| 别名 | 托西尼布磷酸盐,SU11654 phosphate; PHA 291639E phosphate | ||
| Canonical SMILES | O=C(NCCN1CCCC1)C2=C(NC(/C=C3C(NC4=C\3C=C(C=C4)F)=O)=C2C)C.O=P(O)(O)O | ||
| 分子式 | C22H28FN4O6P | 分子量 | 494.45 |
| 溶解度 | DMSO: 2.46 mg/mL (4.98 mM and warming); Water: < 0.1 mg/mL (insoluble) | 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 | 2.0224 mL | 10.1122 mL | 20.2245 mL |
| 5 mM | 0.4045 mL | 2.0224 mL | 4.0449 mL |
| 10 mM | 0.2022 mL | 1.0112 mL | 2.0224 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。
The role of Toceranib phosphate in dogs with non-mast cell neoplasia: A systematic review
Vet Comp Oncol 2022 Jun;20(2):362-371.PMID:34981886DOI:10.1111/vco.12799.
The use of tyrosine kinase inhibitors (TKI) has gained significant importance in veterinary cancer patients over the last decade. Toceranib phosphate has been licensed for the treatment of dogs with mast cell tumours. Its molecular similarity to sunitinib, a TKI used in human medicine, has led many veterinary oncologists to use this agent for multiple neoplastic diseases. The aim of the current study was to perform a systematic review of the evidence for the use of toceranib in dogs with non-mast cell neoplasia. Two electronic databases were searched. Publications were included if toceranib was used as a treatment option in canine patients. Studies and case reports were excluded if toceranib was used as part of a multi-modal treatment plan and response or outcome data related to toceranib therapy were not described. A total of 28 studies were included from 122 references. The most common types of neoplasias identified were neuroendocrine tumours, anal gland sac adenocarcinoma, and osteosarcoma. Multiple other neoplasias had one or two studies identified to describe the use of toceranib. Results of the study support that Toceranib phosphate may have efficacy against certain types of neoplasia under certain conditions, such as neuroendocrine tumours, gastrointestinal stromal tumours and anal sac adenocarcinomas, while it is probably not effective for the management of metastatic osteosarcoma based on the findings of the review.
Toceranib phosphate in the management of canine insulinoma: A retrospective multicentre study of 30 cases (2009-2019)
Vet Rec Open 2022 Jan 20;9(1):e27.PMID:35079406DOI:10.1002/vro2.27.
Background: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi-receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs. Methods: A retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib. Results: Records for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression-free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported. Conclusions: Most dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.
Assessment of postoperative adjuvant treatment using Toceranib phosphate against adenocarcinoma in dogs
J Vet Intern Med 2020 May;34(3):1272-1281.PMID:32267594DOI:10.1111/jvim.15768.
Background: Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery. Objectives: To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor-infiltrating regulatory T cells (Tregs), and intratumoral hypoxia. Animals: Ninety-two client-owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma. Methods: Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor-2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia-inducible factor (HIF)-1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries. Results: Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65-0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF-1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries. Conclusions and clinical importance: Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.
Retrospective evaluation of canine heart base tumours treated with Toceranib phosphate (Palladia): 2011-2018
Vet Comp Oncol 2019 Dec;17(4):465-471.PMID:31069932DOI:10.1111/vco.12491.
Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of Toceranib phosphate for dogs with HBT. Twenty-eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty-seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis. Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68-1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77-679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that Toceranib phosphate is a well-tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease.
Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009-2018)
Vet Comp Oncol 2020 Dec;18(4):519-527.PMID:32012432DOI:10.1111/vco.12571.
Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy- settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings.