Gamitrinib TPP hexafluorophosphate
目录号 : GC32766
GamitrinibTPPhexafluorophosphate是一种Gamitrinib(GA)线粒体基质的抑制剂。
Cas No.:1131626-47-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Human glioblastoma cell lines LN229 (p53 mutant; PTEN, WT), U87 (p53 WT; PTEN mutant), U251 (p53 mutant), prostate adenocarcinoma PC3, breast adenocarcinoma MCF-7, and human epithelial kidney (HEK) 293T are seeded in triplicate onto 96-well plates at 2×103 cells/well, treated with vehicle, Gamitrinib TPP (5, 10, 15, and 20 uM), or nontargeted 17-AAG ( 0-20 μM) for up to 24 h, and quantified for metabolic activity by a MTT colorimetric assay with absorbance at 405 nm. For determination of apoptosis, control or treated tumor cell types (1×106) are labeled for annexin V and propidium iodide (PI) and analyzed by multiparametric flow cytometry. For Gamitrinib TPP-TRAIL combination studies, tumor cell types are simultaneously incubated with suboptimal concentrations of Gamitrinib TPP at 5 μM and TRAIL depending on the cell type at 100 ng/mL (U87), 20 ng/mL (U251), 40 ng/mL (PC3, MCF-7, FHAS), or 200 ng/mL (LN229), and analyzed after 16 h for cell viability by MTT[1]. |
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Animal experiment: |
Mice[1]U87 glioblastoma cells stably transfected with a luciferase expression plasmid (U87-Luc) are suspended in sterile PBS, pH 7.2, and stereotactically implanted (1×105) in the right cerebral striatum of immunocompromised nude mice. Animals with established tumors are randomized in 4 groups (4 animals/group) and started on sterile vehicle (cremophor), TRAIL alone, Gamitrinib TPP alone, or the combination of TRAIL plus Gamitrinib TPP. In all animal groups, TRAIL is injected stereotactically in the right cerebral striatum (2 ng on days 7 and 10 after implantation), and Gamitrinib TPP is given systemically (10 mg/kg as daily i.p. injections on days 6, 7, 9, and 10 after implantation). Treatment is suspended on day 10 after tumor implantation, and tumor growth is assessed weekly by bioluminescence imaging after i.p injection of 110 mg/kg D-luciferin. In some experiments, nude mice carrying established U87-Luc intracranial glioblastomas are treated with systemic Gamitrinib TPP monotherapy at 20 mg/kg as daily i.p. injections and monitored for tumor growth by bioluminescence imaging. Animal survival is calculated per group[1]. |
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References: [1]. Markus D. Siegelin, et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011 Apr 1; 121(4): 1349–1360. |
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Gamitrinib TPP hexafluorophosphate is a Gamitrinib (GA) mitochondrial matrix inhibitor.
Gamitrinib TPP (GamitrinibTPP, G-TPP), a small molecule that combines the Hsp90 ATPase inhibitory module of 17-allylamino geldanamycin (17-AAG) with the mitochondrial-targeting moiety of triphenylphosphonium. Gamitrinib TPP is selectively delivered to mitochondria and does not affect Hsp90 homeostasis outside the organelle. Within a 16-hour exposure, concentrations of Gamitrinib TPP of 15-20 μM indistinguishably kill patient-derived and cultured glioblastoma cell lines. This cell death response has the hallmarks of mitochondrial apoptosis, with loss of organelle inner membrane potential, release of cytochrome c in the cytosol, activation of initiator caspase-9 and effector caspase-3 and caspase-7, and cellular reactivity for annexin V[1].
Whether the combination of TRAIL plus Gamitrinib TPP (GamitrinibTPP, G-TPP) has activity against glioblastoma in vivo is studied. Luciferase-expressing U87 glioblastoma cells implanted in the right cerebral striatum of immunocompromised mice give rise to rapidly growing tumors by bioluminescence imaging, and treatment of these mice with vehicle, stereotactic delivery of TRAIL, or systemic administration of suboptimal concentrations of Gamitrinib TPP does not affect tumor growth in vivo. Similarly, systemic monotherapy with Gamitrinib TPP at concentrations (20 mg/kg as daily i.p. injections) that inhibit subcutaneous xenograft tumor growth in mice has no effect on orthotopic glioblastoma growth. In contrast, 2 cycles of intracranial TRAIL combined with systemic Gamitrinib TPP suppresses the growth of established glioblastomas, with no significant animal weight loss throughout treatment[1].
[1]. Markus D. Siegelin, et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011 Apr 1; 121(4): 1349-1360.
| Cas No. | 1131626-47-5 | SDF | |
| Canonical SMILES | O=C(C=C1NC(/C(C)=C/C=C/[C@H](OC)[C@@H](OC(N)=O)/C(C)=C/[C@H](C)[C@H]2O)=O)C(NCCCCCC[P+](C3=CC=CC=C3)(C4=CC=CC=C4)C5=CC=CC=C5)=C(C[C@H](C[C@@H]2OC)C)C1=O.F[P-2](F)(F)(F)(F)F | ||
| 分子式 | C52H65F6N3O8P2 | 分子量 | 1036.03 |
| 溶解度 | DMSO: 50 mg/mL (48.26 mM) | 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 | 0.9652 mL | 4.8261 mL | 9.6522 mL |
| 5 mM | 0.193 mL | 0.9652 mL | 1.9304 mL |
| 10 mM | 0.0965 mL | 0.4826 mL | 0.9652 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。