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

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.

A 83-01 Chemical Structure

Cas No.: 909910-43-6

Taille Prix Stock Qté
1mg
28,00 $US
En stock
5mg
42,00 $US
En stock
10mg
68,00 $US
En stock
50mg
203,00 $US
En stock
100mg
315,00 $US
En stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Avis des clients

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

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 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.

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
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.

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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Avis

Review for A 83-01

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for A 83-01

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.