SB525334

SB525334 is 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 IC(50) of 14.3 nM and was approximately 4-fold less potent as an inhibitor of ALK4 (IC(50) = 58.5 nM). SB-525334 was inactive as an inhibitor of ALK2, ALK3, and ALK6 (IC(50) > 10,000 nM). In cell-based assays, SB-525334 (1 microM) blocked TGF-beta1-induced phosphorylation and nuclear translocation of Smad2/3 in renal proximal tubule cells and inhibited TGF-beta1-induced increases in plasminogen activator inhibitor-1 (PAI-1) and procollagen alpha1(I) mRNA expression in A498 renal epithelial carcinoma cells.

Product information

CAS Number: 356559-20-1

Molecular Weight: 343.42

Formula: C21H21N5

Chemical Name: 6-(2-(tert-butyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline

Smiles: CC1=CC=CC(=N1)C1NC(=NC=1C1=CC2=NC=CN=C2C=C1)C(C)(C)C

InChiKey: DKPQHFZUICCZHF-UHFFFAOYSA-N

InChi: InChI=1S/C21H21N5/c1-13-6-5-7-16(24-13)19-18(25-20(26-19)21(2,3)4)14-8-9-15-17(12-14)23-11-10-22-15/h5-12H,1-4H3,(H,25,26)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SB525334 (1 μM; for 15 minutes before stimulating with 0.625 ng/ml of TGF-β1, assesses after 6 days) inhibits TGF-β1-mediated proliferation of familial idiopathic pulmonary arterial hypertension (iPAH) pulmonary artery smooth muscle cells (PASMCs) at an IC50 of 295 nM.

In Vivo:

SB525334 (3-30 mg/kg; p.o.; daily from days 17 to 35) significantly reverses pulmonary arterial pressure in a rat model of pulmonary arterial hypertension (PAH).

References:

1. Ying WZ, Aaron KJ, Sanders PW. Transforming growth factor-β regulates endothelial function during high salt intake in rats. Hypertension. 2013 Nov;62(5):951-6. doi: 10.1161/HYPERTENSIONAHA.113.01835. Epub 2013 Sep 16. PubMed PMID: 24041947.
2. Walshe TE, dela Paz NG, D'Amore PA. The role of shear-induced transforming growth factor-β signaling in the endothelium. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2608-17. doi: 10.1161/ATVBAHA.113.302161. Epub 2013 Aug 22. PubMed PMID: 23968981.
3. 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. PubMed PMID: 22399597; PubMed Central PMCID: PMC3508670.

Products are for research use only. Not for human use.