Ro 48-8071 fumarate is an inhibitor of OSC (Oxidosqualene cyclase; IC50=6.5 nM) that has low-density lipoprotein (LDL) cholesterol lowering activity.
Ro 48-8071 fumarate 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human umbilical vein endothelial cells (HUVECs)
1 µM
18-24 hours
To evaluate the effect of Ro 48-8071 on endothelial cell migration and adhesion. Results showed that Ro 48-8071 significantly inhibited both VEGF-induced and baseline EC migration (by 52% and 57%, respectively) and significantly inhibited EC adhesion to different extracellular matrices (e.g., vitronectin, fibronectin, and collagen I) (by 61%, 58%, and 52%, respectively). Additionally, Ro 48-8071 significantly suppressed tube formation in the Matrigel assay (by 70%).
Sci Rep. 2015 Mar 12;5:9054
Normal AG11132A mammary cells
up to 10 µM
24 hours
To determine the effect of RO 48-8071 on the viability of normal mammary cells, concentrations up to 10 μM had no effect on normal cells.
Neurol Neuroimmunol Neuroinflamm. 2021 Oct 12;8(6):e1091.
HepG2 cells
0.113 µM (EC50)
24 hours
To evaluate the effects of Ro 48-8071 on PXR-responsive reporter expression. Results showed that Ro 48-8071 significantly activated PXR-responsive reporter expression.
Drug Metab Dispos. 2009 Apr;37(4):900-8.
Primary cultured human hepatocytes
3, 10, 30 µM
24 hours
To evaluate the effects of Ro 48-8071 on CYP3A4 and CYP2B6 mRNA content. Results showed that Ro 48-8071 treatment significantly increased CYP3A4 and CYP2B6 mRNA levels.
Drug Metab Dispos. 2009 Apr;37(4):900-8.
ZR-75 cells
11.04 ± 0.29 µM (24 h), 7.63 ± 0.30 µM (48 h)
24 hours and 48 hours
To determine the effect of RO 48-8071 on the viability of ZR-75 cells, the IC50 values were found to be 11.04 ± 0.29 μM at 24 h and 7.63 ± 0.30 μM at 48 h.
Breast Cancer Res Treat. 2014 Jul;146(1):51-62
HCC-1428 cells
14.64 ± 0.42 µM (24 h), 11.58 ± 0.34 µM (48 h)
24 hours and 48 hours
To determine the effect of RO 48-8071 on the viability of HCC-1428 cells, the IC50 values were found to be 14.64 ± 0.42 μM at 24 h and 11.58 ± 0.34 μM at 48 h.
Breast Cancer Res Treat. 2014 Jul;146(1):51-62
MCF-7 cells
12.32 ± 0.59 µM (24 h), 6.34 ± 0.34 µM (48 h)
24 hours and 48 hours
To determine the effect of RO 48-8071 on the viability of MCF-7 cells, the IC50 values were found to be 12.32 ± 0.59 μM at 24 h and 6.34 ± 0.34 μM at 48 h.
Breast Cancer Res Treat. 2014 Jul;146(1):51-62
T47-D cells
11.53 ± 0.36 µM (24 h), 7.76 ± 0.29 µM (48 h)
24 hours and 48 hours
To determine the effect of RO 48-8071 on the viability of T47-D cells, the IC50 values were found to be 11.53 ± 0.36 μM at 24 h and 7.76 ± 0.29 μM at 48 h.
Breast Cancer Res Treat. 2014 Jul;146(1):51-62
BT-474 cells
9.51 ± 0.05 µM (24 h), 6.06 ± 0.23 µM (48 h)
24 hours and 48 hours
To determine the effect of RO 48-8071 on the viability of BT-474 cells, the IC50 values were found to be 9.51 ± 0.05 μM at 24 h and 6.06 ± 0.23 μM at 48 h.
Breast Cancer Res Treat. 2014 Jul;146(1):51-62
PANC-1 cells
1, 3, 10, 30, 100 µM
24, 48, 72 hours
RO inhibited PANC-1 cell viability in a dose- and time-dependent manner. The inhibitory ratio was approximately 40% at 10 µM after 72 h and 80% at 30 and 100 µM.
Ro 48-8071 significantly inhibited MQ-4 biosynthesis, reducing it by 88.2 ± 11%, while UQ increased by 30 ± 5%.
FEBS Lett. 2010 Dec 1;584(23):4761-4768
Helix lucorum neurons
2 µM
60 minutes
Ro 48-8071 2 μM decreased the average rate of ACh-induced current depression and did not change the level of spontaneous recovery. The ACh-current amplitude declined constantly in time and did not reach the steady-state level.
Cell Mol Neurobiol. 2017 Nov;37(8):1443-1455
Pancreatic ductal adenocarcinoma cells (HPAF-II)
1 µM
9 hours
To evaluate the effect of Ro 48-8071 on Akt and ERK phosphorylation in HPAF-II cells. Results showed that Ro 48-8071 significantly inhibited Akt and ERK phosphorylation.
Sci Rep. 2015 Mar 12;5:9054
Colon cancer cells (HCT116)
1 µM
9 hours
To evaluate the effect of Ro 48-8071 on Akt and ERK phosphorylation in HCT116 cells. Results showed that Ro 48-8071 significantly inhibited Akt and ERK phosphorylation.
Sci Rep. 2015 Mar 12;5:9054
Ro 48-8071 fumarate 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
RIP-Tag2 transgenic mouse model (spontaneous neuroendocrine pancreatic tumor model), HCT116 human colon carcinoma xenograft model, HPAF-II human pancreatic ductal adenocarcinoma xenograft model
Oral
10 mg/kg/dayaily
Once daily for 4 weeks (RIP-Tag2 model) or 2 weeks (HCT116 and HPAF-II models)
To evaluate the effect of Ro 48-8071 on tumor growth, angiogenesis, and metastasis. Results showed that Ro 48-8071 significantly inhibited tumor growth in RIP-Tag2 mice (by 40%) and significantly reduced tumor volume in HCT116 and HPAF-II xenograft models (by 46% and 47%, respectively). Additionally, Ro 48-8071 significantly reduced lung metastasis in the HCT116 model (number and incidence reduced by 81% and 53%, respectively) and liver metastasis in the HPAF-II model (incidence and number reduced by 75% and 60%, respectively). Ro 48-8071 also significantly reduced tumor vessel area (by 49%, 67%, and 56% in RIP-Tag2, HCT116, and HPAF-II, respectively) and increased pericyte coverage (by 44%, 33%, and 31% in RIP-Tag2, HCT116, and HPAF-II, respectively). Furthermore, when combined with 5-fluorouracil (5-FU), Ro 48-8071 significantly enhanced anti-tumor and anti-metastatic effects (tumor growth inhibition by 71%, lung metastasis incidence and number reduced by 83% and 89%, respectively).
Sci Rep. 2015 Mar 12;5:9054
BALB/c mice
BALB/c mice
Oral
20 mg/day/kg
Daily, for 7 to 21 days
Ro 48-8071 led to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the small intestine. Hepatic cholesterol synthesis was markedly suppressed initially but rebounded to higher than baseline rates within 7 days. Whole body cholesterol synthesis, fractional cholesterol absorption, and fecal neutral and acidic sterol excretion were not consistently changed.
To assess the potential of Ro 48-8071 in preventing cholesterol cholelithiasis in C57L/J mice. Results showed that Ro 48-8071 significantly reduced gallstone prevalence and increased biliary phospholipid secretion rates.
Gut. 2004 Jan;53(1):136-42
BALB/c nude mice
Subcutaneous tumor xenograft model
Intravenous injection
5 mg/kg/day
Once daily for the first 5 days, then once every other day for six more injections
RO significantly inhibited subcutaneous tumor growth in nude mice, with marked reductions in tumor volume and weight.
Mol Med Rep. 2021 Dec;24(6):828
Nude mice
BT-474 tumor xenografts
Intravenous injection
5 or 10 mg/kg
Daily for 5 days, followed by an injection every other day for five additional treatments and then a final injection 2 h prior to sacrifice
To evaluate the effect of RO 48-8071 on BT-474 tumor xenografts, RO significantly suppressed tumor growth with no apparent toxicity.
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