Gamitrinib TPP
目录号 : GC33030
Gamitrinib TPP是一种Gamitrinib（GA）线粒体基质抑制剂。Gamitrinib TPP是一种线粒体靶向HSP90抑制剂，具有抗癌活性，用于化学干扰线粒体蛋白质折叠并诱导线粒体自噬诱导。
Cas No.:1131626-46-4
Sample solution is provided at 25 µL, 10mM.
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Gamitrinib TPP is a Gamitrinib (GA) mitochondrial matrix inhibitor[1]. Gamitrinib TPP is a mitochondrial-targeted HSP90 inhibitor with anticancer activity used to chemically interfere with mitochondrial protein folding and induce mitophagy[2, 3].
In vitro, Gamitrinib TPP (10μM) treatment of HeLa cells stably expressing EGFP-Parkin for 4h and 8h induced Parkin (an E3 ubiquitin ligase) translocation in a time-dependent manner, induced mitophagy, and increased NP40 and SDS-insoluble proteins in mitochondria[4]. Gamitrinib TPP (15-20μM) treatment of glioblastoma cell lines (LN229, U251, U87 cells) for 16h concentration-dependently inhibited cell viability and induced mitochondrial apoptosis and autophagy[5].
In vivo, Gamitrinib TPP (5mg/kg) treated with intraperitoneal injection for 3 weeks in mice bearing a human glioma xenograft model partially inhibited tumor growth, and combined treatment with OTX015 significantly inhibited tumor growth and caused tumor regression[6].
References:
[1] Kang B H, Siegelin M D, Plescia J, et al. Preclinical characterization of mitochondria-targeted small molecule hsp90 inhibitors, gamitrinibs, in advanced prostate cancer[J]. Clinical Cancer Research, 2010, 16(19): 4779-4788.
[2] Wei S, Yin D, Yu S, et al. Antitumor activity of a mitochondrial-targeted HSP90 inhibitor in gliomas[J]. Clinical Cancer Research, 2022, 28(10): 2180-2195.
[3] Hayat U, Elliott G T, Olszanski A J, et al. Feasibility and safety of targeting mitochondria for cancer therapy–preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor[J]. Cancer biology & therapy, 2022, 23(1): 117-126.
[4] Fiesel F C, James E D, Hudec R, et al. Mitochondrial targeted HSP90 inhibitor Gamitrinib-TPP (G-TPP) induces PINK1/Parkin-dependent mitophagy[J]. Oncotarget, 2017, 8(63): 106233.
[5] Siegelin M D, Dohi T, Raskett C M, et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells[J]. The Journal of clinical investigation, 2011, 121(4): 1349-1360.
[6] Ishida C T, Shu C, Halatsch M E, et al. Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in glioblastoma[J]. Oncotarget, 2017, 8(23): 37140.
Gamitrinib TPP是一种Gamitrinib（GA）线粒体基质抑制剂[1]。Gamitrinib TPP是一种线粒体靶向HSP90抑制剂，具有抗癌活性，用于化学干扰线粒体蛋白质折叠并诱导线粒体自噬诱导[2, 3]。
在体外，Gamitrinib TPP（10μM）处理稳定表达EGFP-Parkin的HeLa细胞4h和8h，时间依赖性地诱导了Parkin（一种E3泛素连接酶）易位，诱导了线粒体自噬，增加了细胞线粒体中NP40和SDS不溶性蛋白[4]。Gamitrinib TPP（15-20 μM）处理胶质母细胞瘤细胞系（LN229、U251、U87细胞）16h，浓度依赖性地抑制了细胞活力，诱导了线粒体凋亡和自噬[5]。
在体内，Gamitrinib TPP（5mg/kg）通过腹腔注射治疗人类神经胶质瘤异种移植模型小鼠3周，部分抑制了肿瘤生长，与OTX015联合治疗显著抑制了肿瘤生长，并引起肿瘤消退[6]。
| Cell experiment [1]: | |
Cell lines | HeLa cells |
Preparation Method | HeLa cells stably expressing EGFP-Parkin were seeded in optical plates, treated with 10μM Gamitrinib TPP for 4h or 8h. The effect of Gamitrinib TPP on Parkin translocation was analyzed using high-content imaging (HCI). |
Reaction Conditions | 10μM; 4h or 8h |
Applications | Gamitrinib TPP treatment robustly induced Parkin translocation over time. |
| Animal experiment [2]: | |
Animal models | Nu/Nu mice |
Preparation Method | Nu/Nu mice were implanted subcutaneously with 1×106 LN229 glioblastoma cells. After tumor formation, groups were formed. Mice were treated intraperitoneally with vehicle, OTX015 (50mg/kg), Gamitrinib TPP (5mg/kg) or both agents (5 days on, 2 days off in week 1 and 2; 3 times a week in week 3 for 3 weeks). Tumor growth curves show the development of tumor size for each treatment group. |
Dosage form | 5mg/kg, 5 days on, 2 days off in week 1 and 2; 3 times a week in week 3 for 3 weeks; i.p. |
Applications | Gamitrinib-TPP and OTX015 monotherapy only partially inhibited tumor growth, while combination treatment with Gamitrinib-TPP and OTX015 significantly inhibited tumor growth and caused tumor regression. |
References: | |
| Cas No. | 1131626-46-4 | 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 | ||
| 分子式 | C52H65N3O8P | 分子量 | 891.06 |
| 溶解度 | Soluble 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 | 1.1223 mL | 5.6113 mL | 11.2226 mL |
| 5 mM | 0.2245 mL | 1.1223 mL | 2.2445 mL |
| 10 mM | 0.1122 mL | 0.5611 mL | 1.1223 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。
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Quality Control & SDS
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- Purity: >98.50%
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- SDS (Safety Data Sheet)
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