TH588 |
Catalog No.GC12716
One-Click Copy Product Info
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TH588 is an inhibitor of MTH1 (NUDT1; IC50=5nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1609960-31-7
Sample solution is provided at 25 µL, 10mM.
TH588 is an inhibitor of MTH1 (NUDT1; IC50=5nM)[1-2]. TH588 works by inhibiting MTH1 to prevent cancer cells from clearing oxidized nucleotides, thereby inducing DNA damage and activating the ATM-p53-mediated cell death response and DNA repair. TH588 can be used in research related to lung adenocarcinoma, breast cancer, colon cancer, and melanoma[3-4].
In vitro, TH588 (5-30µM) was used to treat cell lines such as U2OS, HeLa, and RPE-1 for 0 to 4 hours. By inhibiting tubulin polymerization and microtubule dynamics, TH588 significantly suppressed microtubule turnover within the mitotic spindle, leading to chromosome congression defects. TH588 resulted in mitotic arrest, cell death, or cell division with incorrectly aligned chromosomes[5]. TH588 (1–8µM) was applied to H460 human lung cancer cells, U2OS osteosarcoma cells, HeLa, and other cell lines for 0 to 48 hours. TH588 significantly prolonged the duration of mitosis and, by activating the USP28-p53-mediated mitotic surveillance pathway, caused cell cycle arrest in the G1 phase of the subsequent cycle[6].
In vivo, TH588 (50µM) and the photosensitizer Ce6 (20µM) were co-loaded into the nanocarrier T&C@SCLMs. This formulation was administered via tail vein injection (0.2ml; once every 5 days; for a total of 20 days) to nude mice bearing A431 solid tumors. TH588 significantly enhanced the efficacy of photodynamic therapy (PDT), resulting in reduced tumor volume and inducing a higher proportion of tumor cell apoptosis[7]. TH588 (30mg/kg) was administered via daily subcutaneous injection for 2 to 3 weeks to BALB/c-nu nude mice bearing xenografts of MCF7, MDA-MB-231, or MDA-MB-453 human breast cancer cells. TH588 significantly suppressed tumor growth without causing significant hematological or liver function toxicity[8].
References:
[1] Gad H, Koolmeister T, Jemth AS, et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014 Apr 10;508(7495):215-21.
[2] Ikejiri F, Honma Y, Kasukabe T, et al. TH588, an MTH1 inhibitor, enhances phenethyl isothiocyanate-induced growth inhibition in pancreatic cancer cells. Oncol Lett. 2018 Mar;15(3):3240-3244.
[3] Wang JY, Jin L, Yan XG, et al. Reactive Oxygen Species Dictate the Apoptotic Response of Melanoma Cells to TH588. J Invest Dermatol. 2016 Nov;136(11):2277-2286.
[4] Pompsch M, Vogel J, Classen F, et al. The presumed MTH1-inhibitor TH588 sensitizes colorectal carcinoma cells to ionizing radiation in hypoxia. BMC Cancer. 2018 Nov 29;18(1):1190.
[5] Rajendraprasad G, Eibes S, Boldú CG, et al. TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic Spindle. Cancers (Basel). 2021 Nov 29;13(23):5995.
[6] Gul N, Karlsson J, Tängemo C, et al. The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway. Sci Rep. 2019 Oct 11;9(1):14667.
[7] Zhao L, Li J, Su Y, et al. MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy. Sci Adv. 2020 Mar 4;6(10):eaaz0575.
[8] Zhang X, Song W, Zhou Y, et al. Expression and function of MutT homolog 1 in distinct subtypes of breast cancer. Oncol Lett. 2017 Apr;13(4):2161-2168.
| Cell experiment [1]: | |
Cell lines | H460 human lung cancer cells, U2OS osteosarcoma cells, and HeLa cells |
Preparation Method | Cells were maintained in Dulbecco's modified eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and antibiotics at 37°C, 5% CO₂. Cells were treated with TH588 (1-8μM) for 0-48 hours. |
Reaction Conditions | 1-8μM; 0-48 hours. |
Applications | TH588 rapidly reduced microtubule plus-end mobility, disrupted mitotic spindle assembly and chromosome congression, and prolonged mitosis in a concentration-dependent manner. TH588 activated the USP28-p53 mitotic surveillance pathway, leading to cell cycle arrest in the G1 phase of the subsequent cycle. These effects were independent of its intended target, MTH1 inhibition. |
| Animal experiment [2]: | |
Animal models | Female BALB/c-nu nude mice with MCF7, MDA-MB-231, or MDA-MB-453 human breast cancer cell xenografts |
Preparation Method | Mice were inoculated subcutaneously with cancer cells. After tumors reached a visible size (~2mm in mean diameter), mice were administered daily subcutaneous injections of TH588 (30mg/kg) or vehicle control for 2-3 weeks. |
Dosage form | 30mg/kg; s.c.; daily for 2-3 weeks. |
Applications | TH588 treatment significantly suppressed tumor growth, causing over 90% regression in MCF7 and MDA-MB-231 tumors and completely eradicating MDA-MB-453 tumors. TH588 also inhibited mouse body weight gain, although no significant hematological or liver function toxicity was observed. |
References: | |
| Cas No. | 1609960-31-7 | SDF | |
| Chemical Name | (Z)-N-(6-(2,3-dichlorophenyl)-2-imino-2,3-dihydropyrimidin-4(1H)-ylidene)cyclopropanamine | ||
| Canonical SMILES | ClC1=CC=CC(C(NC2=N)=C/C(N2)=N/C3CC3)=C1Cl | ||
| Formula | C13H12Cl2N4 | M.Wt | 295.17 |
| Solubility | ≥ 7.38mg/mL 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 | 3.3879 mL | 16.9394 mL | 33.8788 mL |
| 5 mM | 677.6 μL | 3.3879 mL | 6.7758 mL |
| 10 mM | 338.8 μL | 1.6939 mL | 3.3879 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
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
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)