For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>SB505124 is a selective inhibitor of TGFβR for ALK4, ALK5 with IC50 of 129 nM and 47 nM, respectively, also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6.<br>IC50 Value: 47 ± 5 nM (ALK5); 129 ± 11 nM (ALK4) [1]<br>Target: ALK4/5<br>in vitro: SB-505124 was identified as a potent inhibitor of the in vitro kinase activity of ALK5 for its substrate Smad3 with an IC50 of 47 ± 5 nM. This compound was determined to be a reversible ATP competitive inhibitor, because prior incubation of the ALK5 kinase with high concentrations of the inhibitor, followed by dilution to a sub-IC50concentration had no effect on the kinetics of Smad3 phosphorylation (data not shown). SB-505124 demonstrated no toxicity to renal epithelial A498 cells at concentrations up to 100 μM for 48 h. Selectivity of the SB-505124 inhibitor for type I receptors other than ALK5 was first evaluated against ALK4 and ALK2 in vitro. SB-505124 inhibited the closely related ALK4 with an IC50value of 129 ± 11 nM (about 2.5-fold less sensitive than ALK5) but did not inhibit ALK2 at concentrations up to 10 μM [1]. The in vitro drug release study demonstrated 100% drug release within 12 h. The gel did not show cytotoxicity to the cultured rabbit subconjunctival cells by MTT assay [2]. Suppression of pSmad2, CTGF, and α-SMA by SB-505124 was observed in cultured fibroblasts [3].<br>in vivo: In the in vivo rabbit GFS model, the drug was successfully delivered by injection and no severe post-surgical complications were observed [2]. Filtering blebs in the GFS with SB-505124 group were maintained for more than 10 days, and the period of bleb survival was significantly longer than that in controls. IOP levels after surgery seemed to be related to bleb survival. Histologically, subconjunctival cell infiltration and scarring at the surgical site in the GFS with SB-505124 and mitomycin C (MMC) groups were much subsided compared to controls. Suppression of CTGF and α-SMA by SB-505124 was also observed by immunofluorescence [3].<br>Toxicity: N/A<br>Clinical trial: N/A<br></p>
| Catalog Number | I004609 |
| CAS Number | 694433-59-5 |
| Synonyms | 2-[4-(1,3-benzodioxol-5-yl)-2-(1,1-dimethylethyl)-1H-imidazol-5-yl]-6-methyl-pyridine |
| Molecular Formula | C20H21N3O2 |
| Purity | ≥95% |
| Target | TGF-β Receptor |
| Solubility | DMSO 67 mg/mL; Water <1 mg/mL; Ethanol 67 mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 47 ± 5 nM (ALK5); 129 ± 11 nM (ALK4) [1] |
| InChIKey | WGZOTBUYUFBEPZ-UHFFFAOYSA-N |
| Reference | </br>1:Development and validation of an LC-MS/MS method for the determination of SB-505124 in rat plasma: Application to pharmacokinetic study. Jiang J, Zhang Y, Zhang Q, Li Y, Gong T, Zhang Z, Ding R, Sun X.J Pharm Biomed Anal. 2016 Jan 5;117:205-9. doi: 10.1016/j.jpba.2015.09.002. Epub 2015 Sep 3. PMID: 26363490 </br>2:Thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery. Sutariya V, Miladore N, Geldenhuys W, Bhatia D, Wehrung D, Nakamura H.Pharm Dev Technol. 2013 Jul-Aug;18(4):957-62. doi: 10.3109/10837450.2011.647035. Epub 2011 Dec 30. PMID: 22206499 </br>3:SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. DaCosta Byfield S, Major C, Laping NJ, Roberts AB.Mol Pharmacol. 2004 Mar;65(3):744-52. PMID: 14978253 Free Article |
