FT671

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 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:
[1]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.
[2]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.