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A 83-01
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
A 83-01图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
10mg电议
50mg电议

产品介绍
A 83-01 是 TGF-β I 型受体 ALK5 激酶、I 型淋巴结受体 ALK4 和 I 型淋巴结受体 ALK7 的有效抑制剂,抑制 ALK5、ALK4 和ALK7,分别。

Cell lines

Mv1Lu and C2C12 cells

Preparation Method

Cells were pretreated for 1 h with 1uM small molecule inhibitors A 83-01 and then cultured with TGF-β.

Reaction Conditions

1uM A-83-01, 1 h

Applications

The effects of TGF-β inhibitors on cell proliferation were examined. A 83-01 efficiently prevented the growth-inhibitory effects of TGF-β, A-83-01 prevented inhibition of growth of Mv1Lu cells by TGF-β in a dose-dependent fashion. Treatment with 0.3 uM A 83-01 completely blocked the growth-inhibitory effect of TGF-β.

Animal models

M109 cells were inoculated subcutaneously into CDF1 female mice (5 weeks old)

Preparation Method

When the tumor volume reached approximately 100-200 mm3, SL, F-SL, or free DXR was injected intravenously at 8 mg/kg, with or without intraperitoneal injection of 0.5 mg A 83-01/kg. The control group was injected intravenously with saline (0.2 mL/20 g body weight) with intraperitoneal injection of the vehicle (0.1 mL/20 g body weight).

Dosage form

0.5 mg A-83-01/kg,16day

Applications

The liposomal DXR injected group showed a strong antitumor effect in comparison with saline with or without A 83-01 and free DXR treated groups. A 83-01 alone did not show an antitumor effect. F-SL with A 83-01 showed a significantly stronger antitumor effect than F-SL alone on day 7 and days 13 and 16, SL alone on day 7 and days 10 and 13, or SL with A 83-01 on days 7 and 10.

产品描述

A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I nodal receptor ALK4 and type I nodal receptor ALK7, with IC50s of 12 nM,45 nM and 7.5 nM against the transcription induced by ALK5, ALK4 and ALK7, respectively[1].

A 83-01 reduces the level of ALK-5-induced transcription in Mv1Lu cells, also blocks the ALK4-TD and ALK7-TD induced transcription R4-2 cells, and weakly suppresses that induced by constitutively active ALK-6, ALK-2, ALK-3, and ALK-1. A 83-01 (0.03-10 μM) potently prevents the growth-inhibitory effects of TGF-β, and completely inhibits the effect at 3 μM. A 83-01 (1-10 μM) inhibits TGF-β-induced Smad activation in HaCaT cells[1]. A 83-01 (1 μM) decreases cell motility, adhesion and invasion increased by TGF-β1 in HM-1 cells, but does not change cell proliferation[2]. A-83-01-treated retinal pigment epithelium (RPE) failed to differentiate after 7 passages (P7). Exogenous expression of MYCN and OTX2 in conjunction with A 83-01 restored P7-RPE differentiation to a status similar to minimally passaged RPE[5].

When co-administrated F-SL with A 83-01. Intraperitoneally injected A 83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A 83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A 83-01 temporarily changed the tumor vasculature around 3 h post injection. A 83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A 83-01 showed significantly greater antitumor activity than F-SL alone[3]. A 83-01 treatment significantly increased the number of Nkx2.5(+) cardiomyoblasts at baseline and after myocardial injury, resulting in an increase in newly formed cardiomyocytes[6]. Using transgenic Nkx2.5 enhancer-green fluorescent protein (GFP) reporter mice, and isolated cardiac progenitor cells (CPC). A 83-01 was found to induce proliferation mainly through increasing Birc5 expression in the MEK/ERK-dependent pathway[7]. Treatment of rat dermal fibroblast with A 83-01 inhibited transforming growth factor-β1 (TGF-β1)-dependent induction of α-SMA and collagen type I[4].

References:
[1]: Tojo M, Hamashima Y, et,al. The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-beta. Cancer Sci. 2005 Nov;96(11):791-800. doi: 10.1111/j.1349-7006.2005.00103.x. PMID: 16271073.
[2]: Yamamura S, Matsumura N, et,al. The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. Int J Cancer. 2012 Jan 1;130(1):20-8. doi: 10.1002/ijc.25961. Epub 2011 Apr 18. PMID: 21503873.
[3]: Taniguchi Y, Kawano K, et,al. Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-β type I receptor inhibitor. Cancer Sci. 2010 Oct;101(10):2207-13. doi: 10.1111/j.1349-7006.2010.01646.x. Epub 2010 Jul 1. PMID: 20608940.
[4]: Sun X, Kim YH, et,al. Topical application of ALK5 inhibitor A-83-01 reduces burn wound contraction in rats by suppressing myofibroblast population. Biosci Biotechnol Biochem. 2014;78(11):1805-12. doi: 10.1080/09168451.2014.932666. Epub 2014 Jul 10. PMID: 25351330.
[5]:Shih YH, Radeke MJ, et,al. Restoration of Mesenchymal RPE by Transcription Factor-Mediated Reprogramming. Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):430-441. doi: 10.1167/iovs.16-20018. PMID: 28118667.
[6]: Chen WP, Liu YH, et,al. Pharmacological inhibition of TGFβ receptor improves Nkx2.5 cardiomyoblast-mediated regeneration. Cardiovasc Res. 2015 Jan 1;105(1):44-54. doi: 10.1093/cvr/cvu229. Epub 2014 Oct 31. PMID: 25362681; PMCID: PMC4342671.
[7]: Ho YS, Tsai WH,et,al. Cardioprotective Actions of TGFβRI Inhibition Through Stimulating Autocrine/Paracrine of Survivin and Inhibiting Wnt in Cardiac Progenitors. Stem Cells. 2016 Feb;34(2):445-55. doi: 10.1002/stem.2216. Epub 2015 Oct 10. PMID: 26418219.