Tovetumab
(Synonyms: MEDI-575) 目录号 : GC66385
Tovetumab (MEDI-575) 是一种抗 PDGFRα 单克隆抗体，可选择性的阻断 PDGFRα 信号转导。Tovetumab 可用于胶质母细胞瘤和非小细胞肺癌 (NSCLC) 的研究。
Cas No.:1243266-04-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tovetumab (MEDI-575) is an anti-PDGFRα monoclonal antibody that selectively blocks the PDGFRα signal transduction. Tovetumab can be used in the research of glioblastoma and non-small cell lung cancer (NSCLC)[1][2].
Tovetumab (10-100 nM, 1-2 h) binds to PDGFRα on H1703 cells (determined by Alexa647-labeled tovetumab)[1].
Tovetumab (0.001-10 nM, 10 min) inhibits ligand-induced phosphorylation of human PDGFRα in MG-63 cells[2].
Tovetumab (0.001-100 nM, 72 h ) inhibits Ligand-induced proliferation of cancer-associated fibroblasts (CAFs) [2].
Tovetumab (0.6-60 mg/kg, i.v.) blocks the PDGFRα-mediated elimination of PDGF-AA, leading to an increase in circulating PDGF-AA level in Cynomolgus monkeys[1].
Tovetumab (10 mg/kg, i.p., twice a week) inhibits tumor growth in U118 glioma xenografts[2].
| Animal Model: | Cynomolgus monkey[1] |
| Dosage: | 0.6, 6.0, and 60 mg/kg |
| Administration: | Intravenous injection (i.v.) |
| Result: | Induced > 100- fold increases in circulating concentrations of PDGF-AA. |
| Animal Model: | U118 glioma xenografts (CB17 SCID)[2] |
| Dosage: | 10 mg/kg |
| Administration: | Intraperitoneal injection (i.p.), twice per week. |
| Result: | Produced 101% inhibition of tumor growth. |
| Cas No. | 1243266-04-7 | SDF | Download SDF |
| 别名 | MEDI-575 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 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。 | ||
| 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。
A Novel Pharmacodynamic Biomarker and Mechanistic Modeling Facilitate the Development of Tovetumab, a Monoclonal Antibody Directed Against Platelet-Derived Growth Factor Receptor Alpha, for Cancer Therapy
AAPS J 2020 Nov 18;23(1):4.PMID:33210183DOI:10.1208/s12248-020-00523-3.
Tovetumab (MEDI-575) is a fully human IgG2κ monoclonal antibody that specifically binds to human platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor signal transduction by PDGF ligands. The affinity of Tovetumab determined using surface plasmon resonance technology and flow cytometry demonstrated comparable binding affinity for human and monkey PDGFRα. In single and repeat-dose monkey pharmacokinetic-pharmacodynamic (PK-PD) studies, Tovetumab administration resulted in dose-dependent elevation of circulating levels of PDGF-AA, a member of the PDGF ligand family, due to displacement of PDGF-AA from PDGFRα by Tovetumab and subsequent blockade of PDGFRα-mediated PDGF-AA degradation. As such, PDGF-AA accumulation is an indirect measurement of receptor occupancy and is a novel PD biomarker for Tovetumab. The nonlinear PK of Tovetumab and dose-dependent increase in circulating PDGF-AA profiles were well described by a novel mechanistic model, in which Tovetumab and PDGF-AA compete for the binding to PDGFRα. To facilitate translational simulation, the internalization half-lives of PDGF-AA and Tovetumab upon binding to PDGFRα were determined using confocal imaging to be 14 ± 4 min and 30 ± 8 min, respectively. By incorporating PDGFRα internalization kinetics, the model not only predicted the target receptor occupancy by Tovetumab, but also the biologically active agonistic ligand-receptor complex. This work described a novel PD biomarker approach applicable for anti-receptor therapeutics and the first mechanistic model to delineate the in vivo tri-molecular system of a drug, its target receptor, and a competing endogenous ligand, which collectively have been used for optimal dose recommendation supporting clinical development of Tovetumab.