Gamitrinib TPP |
Catalog No.GC33030
One-Click Copy Product Info
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Gamitrinib TPP is a Gamitrinib (GA) mitochondrial matrix inhibitor. Gamitrinib TPP is a mitochondrial-targeted HSP90 inhibitor with anticancer activity used to chemically interfere with mitochondrial protein folding and induce mitophagy.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1131626-46-4
Sample solution is provided at 25 µL, 10mM.
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.
| Cell experiment [1]: | |
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Cell lines |
HeLa cells |
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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). |
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Reaction Conditions |
10μM; 4h or 8h |
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Applications |
Gamitrinib TPP treatment robustly induced Parkin translocation over time. |
| Animal experiment [2]: | |
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Animal models |
Nu/Nu mice |
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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. |
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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. |
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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. |
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References: |
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| 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 | ||
| Formula | C52H65N3O8P | M.Wt | 891.06 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1223 mL | 5.6113 mL | 11.2226 mL |
| 5 mM | 224.5 μL | 1.1223 mL | 2.2445 mL |
| 10 mM | 112.2 μL | 561.1 μL | 1.1223 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)