DS18561882 |
| カタログ番号GC38906 |
DS18561882は新規の経口活性を有するメチレンテトラヒドロ葉酸デヒドロゲナーゼ（MTHFD2）の特異的阻害剤であり、IC50値は0.0063 μMである。
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は新規の経口活性を有するメチレンテトラヒドロ葉酸デヒドロゲナーゼ（MTHFD2）の特異的阻害剤であり、IC50値は0.0063 μMである。
DS18561882（0-10μM; 72時間）は、特異的にMTHFD2活性を阻害し、HCC38乳癌細胞で細胞周期停止を誘導するが、細胞死は誘導しなかった。Chk1阻害剤とDS18561882の併用治療は、相乗的にアポトーシスを誘導する。DS18561882（50μM; 5日間）とペメトレキセドの併用は、肺腺癌（LUAD）細胞において抗腫瘍感受性を増加させ、治療上の利点を提供する。
DS18561882（経口投与; 30, 100, 300 mg/kg; 1日2回）は、MDA-MB-231luc腫瘍マウスにおいて用量依存的に腫瘍成長を抑制し、300 mg/kgの投与で腫瘍が完全に抑制された。DS18561882（100mg/kg; 経口投与）は、PPFIA4発現の増加によって誘発される去勢抵抗性前立腺癌（CRPC）の進行を有意に妨げる。
[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.
細胞実験 [1]: | |
細胞株 | HCC38乳癌細胞 |
準備方法 | 指定された濃度のDS18561882で処理された細胞 |
反応条件 | 0-10μM; 72時間 |
アプリケーション | DS18561882は特異的にMTHFD2の活性を阻害し、HCC38乳癌細胞で細胞周期停止を誘導する。 |
動物実験 [2]: | |
動物モデル | 雌性BALB/cAJcl-nu/nuマウス（MDA-MB-231luc腫瘍モデル） |
準備方法 | 腫瘍を有するマウスにDS18561882を経口投与し、1日2回、11日間投与した。 |
投与形態 | 経口投与; 30, 100, 300 mg/kg; 1日2回 |
アプリケーション | DS18561882は用量依存的に腫瘍成長を抑制し、マウスにおいて300 mg/kgの投与で完全な抑制が観察された。 |
参考文献: [1]: 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. | |
| 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 |
| 溶解度 | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.643 mL | 8.2152 mL | 16.4303 mL |
| 5 mM | 328.6 μL | 1.643 mL | 3.2861 mL |
| 10 mM | 164.3 μL | 821.5 μL | 1.643 mL |
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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.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)
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