| 规格: | 98% |
| 分子量: | 381.69 |
| 包装 | 价格(元) |
| 1mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 200mg | 电议 |
Background:
Liarozole dihydrochloride is a P-450 inhibitor and retinoic acid (RA) metabolizing blocking agent inhibits RA metabolism and thereby increases intracellular RA levels in cells that actively produce RA. Liarozole has been used in the treatment of a variety of conditions characterized by extracellular matrix (ECM) overproduction such as ichthyosis[1].
IC50values for P-450 Inhibitors Liarozole was determined as 4.2 μM, using male rat hepatic microsomes and 3uM retinoic acid as substrate[2]. Liarozole combination with ATRA potently increased the ability of ATRA to induce proline isomerase (Pin1) degradation.Pin1 knockdown suppresses cell proliferation in various human HCC cell lines. When the concentration of ATRA was fixed at 10?μM, Pin1 was degraded in a dose dependent manner depending on increasing concentrations of liarozole, with IC50~24.5?μM[3]
The cumulative tumor growth was significantly slower in Liarozole compared to the control group (p = 0.0001). Both liarozole and tamoxifen when given alone demonstrated anti-tumor effects. However, while tamoxifen lead to tumor shrinkage, liarozole was only able to stop tumor growth. When given in combination, liarozole (80 mg/kg) plus tamoxifen (100 mg/kg) was more effective than liarozole alone (p = 0.0001). There were no significant differences between the two doses of liarozole either when given alone (p = 0.49) or in combination with tamoxifen (p = 0.8)[4]
参考文献:
[1]. Levy G, Malik M, et al. Liarozole inhibits transforming growth factor-β3--mediated extracellular matrix formation in human three-dimensional leiomyoma cultures. Fertil Steril. 2014 Jul;102(1):272-281.e2.
[2]. Ahmad M. Study on cytochrome p-450 dependent retinoic Acid metabolism and its inhibitors as potential agents for cancer therapy. Sci Pharm. 2011 Oct-Dec;79(4):921-35.
[3]. Liao XH, Zhang AL, et al.Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways. Sci Rep. 2017 Mar 6;7:43639.
[4]. Goss PE, Strasser-Weippl K, et al.Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model. BMC Cancer. 2007 Jan 31;7:26.
Protocol:
| Cell experiment [1]: | |
Cell lines | Hepatocellular carcinoma cell line (Huh-7) |
Preparation Method | Huh-7 cells were treated with Liarozole for 72?hours, followed by subjecting cell lysates to immunoblotting with Pin1 antibody. |
Reaction Conditions | 1,5,10,25,50 μM Liarozole for 72 h. |
Applications | Liarozole combination with ATRA potently increased the ability of ATRA to induce proline isomerase (Pin1) degradation.Pin1 knockdown suppresses cell proliferation in various human HCC cell lines. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Sprague Dawley rats were ovariectomized (OVX) 7 days before the start of the experiment. At 21 days of age the animals were weighed and randomized to treatment groups. Liarozole and vehicle hydroxypropyl-β- cyclodextrin were given twice daily by oral gavage. |
Dosage form | 20, 80mg/kg Liarozole, oral gavages |
Applications | The cumulative tumor growth was significantly slower in Liarozole treatment groups compared to the control group.Liarozole was only able to stop tumor growth. When given in combination, liarozole (80 mg/kg) plus tamoxifen (100 mg/kg) was more effective than liarozole alone. |
参考文献: [1]. Liao XH, Zhang AL, et al.Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways. Sci Rep. 2017 Mar 6;7:43639. [2]. Goss PE, Strasser-Weippl K, et al.Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model. BMC Cancer. 2007 Jan 31;7:26. | |
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