The Kruppel-like factors (KLFs) are a family of transcription factors that contain zinc finger, which could regulate various cellular processes including proliferation, differentiation, development and apoptosis [1] . ML264 is an inhibitor of one of the KLF member, the KLF5, with IC50 value of 29 nM [2] . The DLD-1 and HCT116 cells were treated with 10 μmol/L of ML264. For the cell proliferation experiment, a significant decrease in proliferation of both cells lines was observed within 24 hours of incubation. Western blot analysis showed that the protein levels of ERK and KLF5 were decreased in both DLD-1 and HCT116 cells after 72 hours of ML264 treatment. Both cell lines showed a reduction in the level of the transcription factor early growth response 1 (EGR1) which is a direct activator of KLF5 expression. [3] . Similar results could be seen on HCT116 and MDA-MB-468 cell lines [4] . In DLD-1 tumor xenografts nude mice model, the ML264 was injected intraperitoneally for 10 days with 10 mg/kg or 25 mg/kg twice per day, and the tumor growth was significantly inhibited. The expression of the KLF5 and EGR1 in the xenografts from mice was significantly reduced after the ML264 treatment measured by IHC and western blot analysis [3] .
ML264 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SW620 cells
0.001 to 20 μM
24 hours
SR18662 had the highest inhibitory effect on SW620 cells, with an IC50 value about one log unit lower than those for ML264 and SR15006
Mol Cancer Ther. 2019 Nov;18(11):1973-1984
HT29 cells
0.001 to 20 μM
24 hours
SR18662 had the highest inhibitory effect on HT29 cells, with an IC50 value about one log unit lower than those for ML264 and SR15006
Mol Cancer Ther. 2019 Nov;18(11):1973-1984
HCT116 cells
10 μM
24, 48, and 72 hours
SR18662 significantly inhibited cell proliferation and growth, more effective than ML264 or SR15006
Mol Cancer Ther. 2019 Nov;18(11):1973-1984
DLD-1 cells
10 μM
24, 48, and 72 hours
SR18662 significantly inhibited cell proliferation and growth, more effective than ML264 or SR15006
Mol Cancer Ther. 2019 Nov;18(11):1973-1984
MDA-MB-468
10 μM
48 h
Evaluate the effect of ML264 and its derivatives on MDA-MB-468 cell viability
Theranostics. 2017 Jun 11;7(8):2339-2349
HCC1806
10 μM
48 h
Evaluate the effect of ML264 and its derivatives on HCC1806 cell viability
Theranostics. 2017 Jun 11;7(8):2339-2349
MDA-MB-231
10 μM
48 h
Evaluate the effect of ML264 and its derivatives on MDA-MB-231 cell viability
Theranostics. 2017 Jun 11;7(8):2339-2349
HCT116
10 μM
48 h
Evaluate the effect of ML264 and its derivatives on HCT116 cell viability
ML264 alleviated AA-induced abnormal expressions of GPX4 and 4-HNE, and reduced HDAC3 induction
Redox Biol. 2023 Dec;68:102939
HK-2 cells
10 μmol/L
24 hours
ML264 inhibits KLF5 activity, reduces phosphorylation of NF-κB p65, thereby decreasing NLRP3 inflammasome activation and pyroptosis.
Cell Commun Signal. 2024 Mar 21;22(1):187
HCT116 cells
10µM
24, 48, and 72 hours
ML264 significantly inhibited the proliferation of HCT116 cells, with a 15- to 30-fold reduction in live cell numbers after 72 hours.
Mol Cancer Ther. 2016 Jan;15(1):72-83
DLD-1 cells
10µM
24, 48, and 72 hours
ML264 significantly inhibited the proliferation of DLD-1 cells, with a 15- to 30-fold reduction in live cell numbers after 72 hours.
Mol Cancer Ther. 2016 Jan;15(1):72-83
CRC PDOs
10 μM
7 days
ML264 significantly restored oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response, and this effect was achieved by inhibiting the KLF5/Bcl-2/caspase3 signaling pathway.
Cell Death Dis. 2022 Apr 5;13(4):303
ML264 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
APP/PS1 mice
Intraperitoneal injection
5 mg/kg
Every other day for 15 weeks
To study the effect of ML264 on cognitive function and Aβ deposition in AD model mice, it was found that ML264 significantly improved cognitive deficits and reduced Aβ deposition.
ML264 significantly inhibited the growth of DLD-1 xenograft tumors, with a 25 mg/kg twice daily dose showing significant tumor volume reduction as early as 5 days after treatment.
Mol Cancer Ther. 2016 Jan;15(1):72-83
BALB/c nude mice
CRC xenograft tumor model
Intraperitoneal injection
25 mg/kg ML264, 5 mg/kg oxaliplatin
Oxaliplatin once a week, ML264 twice a week, lasting for 14 days
ML264 significantly inhibited tumor growth in xenograft tumors and restored oxaliplatin-induced tumor apoptosis.
Cell Death Dis. 2022 Apr 5;13(4):303
BALB/c nude mice
A2780-olaR xenograft model
Intraperitoneal injection
10 mg/kg
Every two days until the end of the experiment
Evaluate the in vivo therapeutic effect of ML264 on PARPi-resistant ovarian cancer. Results showed that ML264 alone significantly inhibited tumor growth, and the effect was more pronounced when combined with olaparib.
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