FT671 |
رقم الكتالوجGC32786
One-Click Copy Product Info
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FT671 هو مثبط قوي وغير تعاوني وانتقائي لـ USP7 بتركيز IC50 يبلغ 52 نانومترًا ويرتبط بمجال الأساسية الحفزية لـ USP7 بتركيز Kd يبلغ 65 نانومترًا.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| Cell experiment [1]: | |
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Cell lines |
A549 cells |
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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. |
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Reaction Conditions |
0, 2, 4, 8, 16, 24µM; 4h |
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Applications |
FT671 significantly promoted the degradation of both SP1 and β-Catenin in A549 cancer cells. |
| Animal experiment [2]: | |
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Animal models |
Non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice |
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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). |
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Dosage form |
100, 200mg/kg/day; p.o. |
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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. |
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References: |
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| 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 | ||
| Formula | C24H23F4N7O3 | M.Wt | 533.48 |
| الذوبان | DMSO: 50 mg/mL (93.72 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. |
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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 | 1.8745 mL | 9.3724 mL | 18.7448 mL |
| 5 mM | 374.9 μL | 1.8745 mL | 3.749 mL |
| 10 mM | 187.4 μL | 937.2 μL | 1.8745 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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 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
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)