SB-505124 hydrochloride

Research use only, not for human use.

SB-505124 hydrochloride (SB505124 hydrochloride) is an orally available, selective and potent inhibitor of TGF-β type I receptors (ALK4, ALK5, ALK7) with IC50 values of 129 nM and 47 nM for ALK4 and ALK5, respectively.

SB-505124 hydrochloride is a selective inhibitor of?TGF-β Receptor type I receptor (ALK4, ALK5, ALK7), with?IC50s?of 129 nM and 47 nM for?ALK4, ALK5, respectively, but it does not inhibit ALK1, 2, 3, or 6.

SB-505124 demonstrates no toxicity to renal epithelial A498 cells at concentrations up to 100 μM for 48 h. 505124 inhibits the closely related ALK4 with an IC50 value of 129±11 nM (about 2.5-fold less sensitive than ALK5) but does not inhibit ALK2 at concentrations up to 10 μM. SB-505124 (1 μM) inhibits the TGF-β-induced phosphorylation of Smad2 in all three of these cell lines in a concentration-dependent fashion. SB-505124 (1 or 5 μM) potently inhibits TGF-β-induced activation of JNK/SAP, extracellular signal-regulated kinase 1/2, and p38 despite the different patterns of activation in these cells. SB-505124 (10 μM) impairs Smad2 phosphorylation and CTGF and α-SMA expression in vitro. SB-505124 susspresses CTGF and α-SMA observed by immunofluorescence. Cell outgrowth from explants dissected from eyes to which SB-505124 is applied during GFS is robust while outgrowth is poor from those treated with MMC.

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.Animal Model:C57Bl6 mice with A549 xenografts 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.

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Angiogenesis

ALK

ALK

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356559-13-2

371.86

C20H22ClN3O2

>98% (HPLC)

In Vitro:?Methanol : 125 mg/mL (336.15 mM; Ultrasonic)DMSO : 50 mg/mL (134.46 mM; Ultrasonic (<60°C); )

Cl.N=1C(=CC=CC1C)C=2N=C(NC2C=3C=CC=4OCOC4C3)C(C)(C)C

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(-20℃)

With Ice Pack

≥ 2 years