SB525334 (Synonyms: TGF-β RI Kinase Inhibitor VIII) |
Catalog No.GC14349
One-Click Copy Product Info
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SB525334 has been characterized as a potent and selective inhibitor of the transforming growth factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). SB525334 inhibited ALK5 kinase activity with an IC50 of 14.3nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 356559-20-1
Sample solution is provided at 25 µL, 10mM.
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SB525334 has been characterized as a potent and selective inhibitor of the transforming growth factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). SB525334 inhibited ALK5 kinase activity with an IC50 of 14.3nM [1].
In vitro, SB525334 (1μM; 16h) effectively attenuated the TGF-β1-induced epithelial to mesenchymal transition (EMT) in HPMCs[2]. In the presence of TGF-β, treatment of 4T1 tumor cells with SB525334 can reverse the pro-metastatic effect of TGF-β[3]. SB525334 (0, 1.25, 2.5, 5 and 10μM; 72h) can reduce gemcitabine resistance in resistant cells (MiaPaCa2 and AsPC1). Additionally, treatment with SB525334 (20μM; 24h) reduced the activity of the AKT signaling pathway, which plays a crucial role in gemcitabine resistance[4].
In vivo, In a mouse model of peritoneal fibrosis, cotreatment with chlorhexidine gluconate (CG) and SB525334 (20mg/kg/day; 28 days; p.o.) improved peritoneal thickness and fibrosis and restored peritoneal function[2]. In a orthotopic metastasis model, administration of SB525334(1mg/kg, 5mg/kg and 10mg/kg/every other day; 28 days; i.v.) significantly unleashed the antitumor response of infiltrating neutrophils[3].
References:
[1] Grygielko ET, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, Laping NJ. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005 Jun;313(3):943-51.
[2] Heo JY, Do JY, Lho Y, Kim AY, Kim SW, Kang SH. TGF-β1 Receptor Inhibitor SB525334 Attenuates the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells via the TGF-β1 Signaling Pathway. Biomedicines. 2021 Jul 19;9(7):839.
[3] Li Y, Hu Q, Li W, Liu S, Li K, Li X, Du J, Yu Z, Wang C, Zhang C. Simultaneous blockage of contextual TGF-β by cyto-pharmaceuticals to suppress breast cancer metastasis. J Control Release. 2021 Aug 10;336:40-53.
[4] Kim YJ, Hwang JS, Hong YB, Bae I, Seong YS. Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine. Anticancer Res. 2012 Mar;32(3):799-806.
| Cell experiment [1]: | |
Cell lines | HPMCs |
Preparation Method | The cytotoxicity of SB525334 was evaluated using the MTT assay. Approximately, 104 HPMCs/well were initially seeded and cultured in 96-well plates for 24h, then treated with SB525334 (0, 0.1, 1, 10, 100 and 200μM) in 200μL media for 24-72h. At the end of the incubation period, 20μL of MTT (5mg/mL) was added to each well and incubated at 37°C for 3.5h. Subsequently, 200μL of DMSO was added to each well to solubilize the formazan products. Absorbance was measured at 570nm using a microplate reader. |
Reaction Conditions | 0, 0.1, 1, 10, 100 and 200μM; 24-72h |
Applications | SB525334 exhibited no significant toxicity at concentrations up to 10μM, but displayed marked toxicity at 100μM. |
| Animal experiment [2]: | |
Animal models | female BALB/c mice |
Preparation Method | For orthotopic metastasis, 1×106 4T1 cells or 4T1-Luc cells suspended in 100μL PBS were injected into the right mammary fat pad of female BALB/c mice (6-8 weeks), and the lung metastasis was monitored by the IVIS Spectrum In Vivo Imaging System. Mice bearing 4T1 spontaneous lung metastasis were randomly divided into four groups receiving i.v. injection of saline and SB525334 at the dosage of 1mg/kg, 5mg/kg and 10mg/kg every other day. On day 28, the mice were sacrificed, and the harvested lungs were subjected to the H&E staining analysis to determine the metastasis-inhibiting efficacy. |
Dosage form | 1mg/kg, 5mg/kg, and 10mg/kg every other day; 28 days; i.v. |
Applications | In a orthotopic metastasis model, administration of SB525334 significantly unleashed the antitumor response of infiltrating neutrophils. |
References: | |
| Cas No. | 356559-20-1 | SDF | |
| Synonyms | TGF-β RI Kinase Inhibitor VIII | ||
| Chemical Name | 6-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]quinoxaline | ||
| Canonical SMILES | CC1=CC=CC(=N1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=NC=CN=C4C=C3 | ||
| Formula | C21H21N5 | M.Wt | 343.42 |
| Solubility | ≥ 34.3mg/mL in DMSO, ≥ 23.8 mg/mL in EtOH | Storage | Store at -20°C |
| 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9119 mL | 14.5594 mL | 29.1189 mL |
| 5 mM | 582.4 μL | 2.9119 mL | 5.8238 mL |
| 10 mM | 291.2 μL | 1.4559 mL | 2.9119 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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.)
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 saline, 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.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 36 reference(s) in Google Scholar.)