DS18561882
目录号 : GC38906
DS18561882是一种新型的口服活性特异性亚甲基四氢叶酸脱氢酶(MTHFD2)抑制剂，IC50值为0.0063 μM。
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]: | |
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Cell lines |
HCC38 breast cancer cells |
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Preparation Method |
Cells treated with indicated concentrations of DS18561882. |
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Reaction Conditions |
0-10μM; 72h |
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Applications |
DS18561882 specifically inhibits the activity of MTHFD2 and induces cell cycle arrest in HCC38 breast cancer cells. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/cAJcl-nu/nu mice(MDA-MB-231luc tumor model) |
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Preparation Method |
The tumor-bearing mice were given DS18561882 orally twice daily for 11 days. |
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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. |
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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 | ||
| 分子式 | C28H31F3N4O6S | 分子量 | 608.63 |
| 溶解度 | DMSO: 250 mg/mL (410.76 mM) | 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 | 1.643 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 |
| 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet