A 83-01 |
Catalog No.GC10166 |
Un inhibiteur du récepteur de type I de TGF-β.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 909910-43-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
A 83-01 est un inhibiteur puissant de la kinase du récepteur de type I TGF-β ALK5, du récepteur nodal de type I ALK4 et du récepteur nodal de type I ALK7, avec des IC50 de 12 nM, 45 nM et 7,5 nM contre la transcription induite par ALK5, ALK4 et ALK7 respectivement [1].
A 83-01 réduit le niveau de transcription induit par ALK-5 dans les cellules Mv1Lu, bloque également la transcription induite par ALK4-TD et ALK7-TD dans les cellules R4-2, et supprime faiblement celle induite par les ALK-6, ALK-2, ALK-3 et ALK-1 constitutivement actifs. A 83-01 (0,03 à 10 μM) empêche puissamment les effets inhibiteurs de croissance du TGF-β et inhibe complètement l'effet à 3 μM. A 83-01 (1 à 10 μM) inhibe l'activation de Smad induite par le TGF-bêta dans les cellules HaCaT [1]. A 83-01 (1 μM) diminue la motilité des cellules, l'adhésion et l'invasion augmentées par le TGF-bêta1 chez les cellules HM -1 mais ne modifie pas la prolifération des cellules [2]. Les épithéliums pigmentaires rétiniens traités avec A -83 -01 n'ont pas réussi à se différencier après sept passages (P7). L'expression exogène de MYCN et OTX2 conjointement avec A 83–01 a restauré la différenciation P7-RPE à un état similaire aux épithéliums pigmentaires rétiniens minimisés en termes de passage [5].
Lors de l'administration concomitante de F-SL avec A 83-01, les altérations induites par l'injection intrapéritonéale d'A 83-01 dans la néovascularisation associée au cancer ont été examinées par imagerie par résonance magnétique (IRM) et analyse histologique. L'efficacité ciblée des injections intraveineuses uniques de F-SL combinées à A 83-01 a été évaluée en mesurant la biodistribution et l'effet antitumoral chez des souris porteuses du carcinome pulmonaire murin M109. A 83-01 a temporairement modifié la vascularisation tumorale environ trois heures après l'injection. A 83-01 a induit une accumulation de médicament F-SL dans la tumeur supérieure d'un facteur de 1,7 par rapport aux liposomes seuls à 24 heures après l'injection. De plus, F-SL co-administré avec A 83-01 a montré une activité antitumorale significativement plus grande que F-SL seul [3]. Le traitement avec A 83-01 a augmenté significativement le nombre de cardiomyoblastes Nkx2.5 (+) à la base et après une blessure myocardique, entraînant une augmentation des cardiomyocytes nouvellement formés [6]. En utilisant des souris transgéniques reporter Nkx2.5 enhancer-green fluorescent protein (GFP), et des cellules progénitrices cardiaques isolées (CPC). On a constaté qu'A 83-01 induisait principalement la prolifération en augmentant l'expression de Birc5 dans la voie dépendante de MEK/ERK [7]. Le traitement des fibroblastes dermiques de rat avec A 83-01 a inhibé l'induction dépendante du facteur de croissance transformant β1 (TGF-β1) d'α-SMA et du collagène de 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.
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 |
Solubility | 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. |
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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