DS18561882 |
| Katalog-Nr.GC38906 |
DS18561882 ist ein hochwirksamer, isoenzym-selektiver Methylenetetrahydrofolat-Dehydrogenase-2 (MTHFD2)-Inhibitor mit einem IC50-Wert von 0,0063 μM. DS18561882 hat auch eine hemmende Wirkung auf MTHFD1 (IC50=0,57 μM). DS18561882 zeigt ein gutes orales pharmakokinetisches Profil.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2227149-22-4
Sample solution is provided at 25 µL, 10mM.
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DS18561882 is a novel, orally active, specific inhibitor of methylenetetrahydrofolate dehydrogenase (MTHFD2), exhibiting an IC50 value of 0.0063 μM[1].
DS18561882(0-10μM; 72h) specifically inhibits MTHFD2 activity and induces cell cycle arrest in HCC38 breast cancer cells, however, it did not induce cell death. Combinatory treatment of Chk1 inhibitor and DS18561882 induces apoptosis synergistically [2]. DS18561882(50 µM; 5days) together with pemetrexed increased the antitumor sensibilities and provided therapeutic advantages in the treatment of Lung adenocarcinoma (LUAD) cells[3].
DS18561882(oral administration; 30, 100 or 300 mg/kg; twice daily) inhibited tumor growth in MDA-MB-231luc tumor mice in a dose-dependent manner, and the tumor was completely suppressed at a dose of 300 mg/kg[1]. DS18561882(100mg/kg; p.o.) can significantly impede the progression of castration-resistant prostate cancer (CRPC) induced by elevated PPFIA4 expression[4].
[1]. Kawai J, Toki T, et,al. Discovery of a Potent, Selective, and Orally Available MTHFD2 Inhibitor (DS18561882) with in Vivo Antitumor Activity. J Med Chem. 2019 Nov 27;62(22):10204-10220. doi: 10.1021/acs.jmedchem.9b01113. Epub 2019 Nov 18. PMID: 31638799.
[2]. Lee J, Chen X, et,al. A novel oral inhibitor for one-carbon metabolism and checkpoint kinase 1 inhibitor as a rational combination treatment for breast cancer. Biochem Biophys Res Commun. 2021 Dec 20;584:7-14. doi: 10.1016/j.bbrc.2021.11.001. Epub 2021 Nov 2. PMID: 34753066.
[3]. Zhao R, Feng T, et,al. PPFIA4 promotes castration-resistant prostate cancer by enhancing mitochondrial metabolism through MTHFD2. J Exp Clin Cancer Res. 2022 Apr 5;41(1):125. doi: 10.1186/s13046-022-02331-3. PMID: 35382861; PMCID: PMC8985307.
| Cell experiment [1]: | |
|
Cell lines |
HCC38 breast cancer cells |
|
Preparation Method |
Cells treated with indicated concentrations of DS18561882. |
|
Reaction Conditions |
0-10μM; 72h |
|
Applications |
DS18561882 specifically inhibits the activity of MTHFD2 and induces cell cycle arrest in HCC38 breast cancer cells. |
| Animal experiment [2]: | |
|
Animal models |
Female BALB/cAJcl-nu/nu mice(MDA-MB-231luc tumor model) |
|
Preparation Method |
The tumor-bearing mice were given DS18561882 orally twice daily for 11 days. |
|
Dosage form |
Oral administration; 30, 100 or 300 mg/kg; twice daily |
|
Applications |
DS18561882 demonstrates dose-dependent inhibition of tumor growth, with complete inhibition observed at a dose of 300 mg/kg in mice. |
|
References: |
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| Cas No. | 2227149-22-4 | SDF | |
| Canonical SMILES | CS(=O)(NC1=CC=C(C(N2CCC(C3=CC=C(N4C[C@H](C)N(C)CC4)C(C)=C3O5)=C(C5=O)C2)=O)C=C1OC(F)(F)F)=O | ||
| Formula | C28H31F3N4O6S | M.Wt | 608.63 |
| Löslichkeit | DMSO: 250 mg/mL (410.76 mM) | 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. |
||
| 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 | 1.643 mL | 8.2152 mL | 16.4303 mL |
| 5 mM | 0.3286 mL | 1.643 mL | 3.2861 mL |
| 10 mM | 0.1643 mL | 0.8215 mL | 1.643 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
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 ddH2O, 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)
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