FT671
目录号 : GC32786
FT671是一种是有效的选择性泛素特异性蛋白酶7（USP7）抑制剂，IC50值为52nM。
Cas No.:1959551-26-8
Sample solution is provided at 25 µL, 10mM.
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FT671 is a potent and selective inhibitor of ubiquitin-specific protease 7 (USP7) with an IC50 value of 52nM[1]. USP7 can deubiquitinate MDM2, resulting in a decrease in the intracellular level of p53[2]. FT671 has anti-tumor activity[3].
In vitro, pretreatment of A549 cells with FT671 (0-24µM) for 4h significantly promoted the degradation of intracellular SP1 and β-Catenin proteins[4]. Treatment of colorectal cancer HCT116 cells with FT671 (10µM) for 5min significantly attenuated intracellular protein ubiquitination under the condition of USP7 knockdown[5].
In vivo, oral treatment of MM.1S cell xenograft mice with FT671 (100, 200mg/kg) significantly inhibited the growth of tumors in mice in a dose-dependent manner and was well tolerated[6].
References:
[1] Tanguturi P, Kim K S, Ramakrishna S. The role of deubiquitinating enzymes in cancer drug resistance[J]. Cancer chemotherapy and pharmacology, 2020, 85(4): 627-639.
[2] Park H B, Baek K H. Current and future directions of USP7 interactome in cancer study[J]. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 2023, 1878(6): 188992.
[3] Cheng Y J, Zhuang Z, Miao Y L, et al. Identification of YCH2823 as a novel USP7 inhibitor for cancer therapy[J]. Biochemical Pharmacology, 2024, 222: 116071.
[4] Zhang K, Sun T, Li W, et al. Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells[J]. Cell Communication and Signaling, 2023, 21(1): 319.
[5] Steger M, Demichev V, Backman M, et al. Time-resolved in vivo ubiquitinome profiling by DIA-MS reveals USP7 targets on a proteome-wide scale[J]. Nature communications, 2021, 12(1): 5399.
[6] Turnbull A P, Ioannidis S, Krajewski W W, et al. Molecular basis of USP7 inhibition by selective small-molecule inhibitors[J]. Nature, 2017, 550(7677): 481-486.
FT671是一种是有效的选择性泛素特异性蛋白酶7（USP7）抑制剂，IC50值为52nM[1]。USP7能将MDM2去泛素化，从而导致p53的细胞内水平下降[2]。FT671具有抗肿瘤活性[3]。
在体外，FT671（0-24µM）预处理A549细胞4h，显著促进了细胞内SP1和β-Catenin蛋白的降解[4]。FT671（10µM）处理结直肠癌HCT116细胞5min，在USP7敲低的条件下，显著减弱了细胞内蛋白质泛素化[5]。
在体内，FT671（100, 200mg/kg）通过口服治疗MM.1S细胞异种移植小鼠，以剂量依赖性方式显著抑制了小鼠体内肿瘤的生长，并具有良好的耐受性[6]。
| Cell experiment [1]: | |
Cell lines | A549 cells |
Preparation Method | A549 cells were pretreated with FT671(0, 2, 4, 8, 16, 24µM) for 4h, and then treated with 50μg/mL cycloheximide (CHX) for 0-24h, and the protein was used for Western blot analysis. |
Reaction Conditions | 0, 2, 4, 8, 16, 24µM; 4h |
Applications | FT671 significantly promoted the degradation of both SP1 and β-Catenin in A549 cancer cells. |
| Animal experiment [2]: | |
Animal models | Non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice |
Preparation Method | 6 to 8-week-old female NOD SCID mice were irradiated (2Gγ) with a Co60 irradiator source 24h prior to subcutaneous inoculation of 5×106 MM.1S tumor cells in 1:1 mixture of RPMI-1640 and Matrigel. The efficacy study was initiated when tumors had reached an average volume of 159 mm3. Tumour-bearing mice were randomly assigned to treatment groups such that each treatment group had the same average tumor volume. Mice received a lead-in dose of 25mg/kg of FT671 24h prior to starting on the dosing regimen of 100 or 200mg/kg FT671 (once a day, per os by oral gavage). 10% DMA/90% PEG400 served as a vehicle control. For the statistical analysis of differences in tumor volumes between treatment groups, a 2-way ANOVA with repeated measures was performed followed by correction for multiple comparisons using statistical hypothesis testing (Tukey). |
Dosage form | 100, 200mg/kg/day; p.o. |
Applications | Treatment of mice with FT671 led to significant dose-dependent tumor growth inhibition. FT671 was well tolerated even at high doses, and no significant weight loss or cachexia was observed during the study. |
References: | |
| Cas No. | 1959551-26-8 | SDF | |
| Canonical SMILES | FC1=CC=C(N2N=CC3=C2N=CN(CC4(O)CCN(C(C[C@@H](C(F)F)N5N=C(F)C=C5)=O)CC4)C3=O)C=C1 | ||
| 分子式 | C24H23F4N7O3 | 分子量 | 533.48 |
| 溶解度 | DMSO: 50 mg/mL (93.72 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 | 1.8745 mL | 9.3724 mL | 18.7448 mL |
| 5 mM | 0.3749 mL | 1.8745 mL | 3.749 mL |
| 10 mM | 0.1874 mL | 0.9372 mL | 1.8745 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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