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AM580

CAS No. : 102121-60-8

MCE 国际站：AM580

产品活性：AM580是选择性的 RARα 激动剂，IC₅₀ 和 EC₅₀ 分别为8 nM，0.36 nM。

研究领域：Metabolic Enzyme/Protease  |  Vitamin D Related/Nuclear Receptor  |  Autophagy

作用靶点：RAR/RXR  |  Autophagy

In Vitro: In the presence of G-CSF, AM580 (at 10^-8 M) produces a remarkable induction in LAP mRNA of NB4 cells. At a concentration of 10^-5 M, AM580 and ATRA, in combination with G-CSF, induce almost the same level of LAP transcript. AM580 (at 10^-8 M) leads to an approximately sixfold increase in the steady-state levels of the transcript coding for the G-CSF receptor in NB4 cells. AM580 (50 nM) increases caspase-3 expression in all of the colonies, and in 30% of the colonies induce acinar-like cavitation. Knockdown of RARγ1 in primary Myc cells using shRARγ1 followed by Am580 treatment results in an even higher level of CRBP1 expression, showing that in these cells RARγ has a repressive effect on the RARα target gene CRBP1. Am580 (200 nM) enhances the anti-proliferative effect exhibited by RARγ knockdown in the MCF-10A and MCF-7 cell lines but not in the MDA-MB-231 cells.

In Vivo: Am580 (0.3 mg/kg/day) treatment has a more profound effect on tumor-free survival of MMTV-wnt1 mice, the effect being noticeable even in early appearing tumors, and no overt toxicity is found in liver, lungs, kidney, and spleen. Am580 treatment reduces substantially and equally the level of hyperplasia in both transgenic glands. Treatment of MMTV-Myc mice with the RARα-selective agonist Am580 leads to significant inhibition of mammary tumor growth, lung metastasis and extends tumor latency in 63% of mice.

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