TGF-beta RI Kinase Inhibitor III is an inhibitor of activin receptor-like kinase 4.
sb505124 is a selective inhibitor of tgfβr for alk4, alk5 with ic50 value of 129 nm and 47 nm [1].anaplastic lymphoma kinase (alk) gets involved in the development of the brain and influence specific neurons in the nervous system.sb505124 is a reversible atp competitive inhibitor of alk4 and alk5. incubation of the alk5 with high concentrations of sb505124, followed by dilution to a sub-ic50 concentration resulted in no effect of downstream smad3 phosphorylation [2]. sb505124 was shown to have no toxicity to renal epithelial a498 cells at concentrations up to 100 μm for 48 h. evidence showed that 100% drug will release within 12 h, and the gel showed no cytotoxicity to the cultured rabbit subconjunctival cells[2]. it was observed that alk4 downstream effectors including psmad2, ctgf, and α-sma was inhibited by sb505124 in cultured fibroblasts [3].in rabbit in glaucoma filtration surgery (gfs) model, the period of filtering blebs were reduced by tgfβ induced fibroblast. the filtering blebs in the gfs with sb505124 group were maintained for more than 10 days, and the period of bleb survival was significantly longer than that in controls, which suggested the significant inhibition of alk4 and 5 by sb505124 [2]. it was observed that alk4 downstream effectors ctgf and α-sma were suppressed by sb-505124 in vivo[3].
SB-505124 (5 mg/kg; i.p.) alone has no effect in C57Bl6 mice with A549 xenografts, but administration of SB-505124 with a single dose of Carboplatin (60 mg/kg) results in durable responses without the need for maintenance therapy in five animals[4].
| Animal Model: | C57Bl6 mice with A549 xenografts[4] |
| Dosage: | 5 mg/kg |
| Administration: | I.p.; daily |
| Result: | Had no effect alone, but administration with a single dose of carboplatin (60 mg/kg) resulted in durable responses without the need for maintenance therapy in five animals. |
[1]. dacosta b s et al. sb-505124 is a selective inhibitor of transforming growth factor-beta type i receptors alk4, alk5, and alk7. mol pharmacol., 2004,65(3): 744-52.
[2]. sutariya v, et al. thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor sb-505124 for glaucoma filtration surgery. pharm dev technol., 2013, 18(4): 957-962.
[3]. sapitro j, et al. suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor. mol vis., 2010, 16: 1880-1892.
