الصفحة الرئيسية>>Signaling Pathways>> TGF-β / Smad Signaling>> TGF-βR1(ALK5)>>A 83-01

A 83-01

رقم الكتالوجGC10166

مثبط مستقبل TGF-β النوع الأول

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A 83-01 التركيب الكيميائي

Cas No.: 909910-43-6

الحجم السعر المخزون الكميّة
1mg
28٫00
متوفر
5mg
42٫00
متوفر
10mg
68٫00
متوفر
50mg
203٫00
متوفر
100mg
315٫00
متوفر

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

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 experiment [2]:

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.

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]. 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.

Background

A 83-01 هو مثبط فعال لمستقبل TGF-β النوع I المسمى ALK5 kinase ومستقبل nodal النوع I المسمى ALK4 ومستقبل nodal النوع I المسمى ALK7، بتراكيز IC50 تصل إلى 12 نانومتر و45 نانومتر و7.5 نانومتر على التوالي ضد التشفير الذي يحفزه ALK5 وALK4 وALK7 [1] .

يقلل A 83-01 من مستوى النسخ الوراثي المحفز بواسطة ALK-5 في خلايا Mv1Lu، كما يحجب نسخ الوراثية المحفزة بواسطة ALK4-TD وALK7-TD في خلايا R4-2، ويكبح ضعفًا تأثيرات التشغيل المستمر لـ ALK-6 وALK-2 وALK-3 وALK-1. يمنع A 83-01 (0.03 - 10 μM) بشكل فعال التأثيرات المثبطة لنمو TGF-beta، كما يُثبِّط هذه التأثيرات تمامًا عند جرعة 3 μM. يُثبِّط A 83-01 (1 - 10 μM) تنشيط Smad الذي يتسبَّب به TGF-beta في خلايا HaCaT [1]. يُقلِّص A 83-01 (1μM) حركية الخلايا، إضافة إلى ارتفاع قابلية التصاقها وغزوها من قِبَل TGF-beta1 في خلايا HM -1، دون أن يؤدي إلى أية تغيرات في انقسام هذه الخلاي [2]. فشلت خلايا الظهارة الصباغية المعالجة بـ A-83-01 في التمايز بعد 7 مراتب (P7). أدى التعبير الخارجي للMYCN و OTX2 جنبًا إلى جنب مع A 83-01 إلى استعادة تمايز P7-RPE إلى حالة مشابهة للظهور الصباغي ذو المرور الأدنى [5].

عند إدارة F-SL مع A 83-01، تم فحص التغيرات المستحثة في الأوعية الدموية المرتبطة بالسرطان باستخدام التصوير بالرنين المغناطيسي (MRI) والتحليل النسجي. تم تقييم كفاءة استهداف الحقن الوريدي لـ F-SL المفرد أو مجتمع مع A 83-01 من خلال قياس التوزُّع الحَیَوِی والتأثير المضاد للورم في فئران حاملة سرطان رئة M109. غير أن A 83-01 غير نظام أوعية دموية حول الورم بشكل مؤقت حول 3 ساعات بعد الحقن. كذلك، يزيد علاج A 83-01 من عدد Nkx2.5 (+) cardiomyoblasts في خلافات دراسات جديده [6]. وباستخدام CPC، اكتشف أن A 83-01 يزود بإضافه Birc5 expression في MEK/ERK-dependent pathway [7]. هذا وأظهر علاج fibroblast dermal rat باستخدام A 83-01 قابضًا لإنتاج transforming growth factor-β1 (TGF-β1) المعتمد على α-SMA و 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.

Chemical Properties

Cas No. 909910-43-6 SDF
Chemical Name 3-(6-methylpyridin-2-yl)-N-phenyl-4-quinolin-4-ylpyrazole-1-carbothioamide
Canonical SMILES CC1=CC=CC(=N1)C2=NN(C=C2C3=CC=NC4=CC=CC=C34)C(=S)NC5=CC=CC=C5
Formula C25H19N5S M.Wt 421.52
الذوبان 100 mg/mL in DMSO (ultrasonic and warming and heat to 45°C), ≥ 9.82 mg/mL in EtOH with ultrasonic and warming Storage -20°C, protect from light, stored under nitrogen,unstable in solution, ready to use.
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.3724 mL 11.8618 mL 23.7237 mL
5 mM 0.4745 mL 2.3724 mL 4.7447 mL
10 mM 0.2372 mL 1.1862 mL 2.3724 mL
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