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SB 431542

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Chemical Structure| 301836-41-9 同义名 : -
CAS号 : 301836-41-9
货号 : A172016
分子式 : C22H16N4O3
纯度 : 99%+
分子量 : 384.387
MDL号 : MFCD05865244
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(273.16 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 10 mg/mL(26.02 mM)，配合低频超声，并水浴加热至45℃助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

2% DMSO+30% PEG 300+water 5 mg/mL

生物活性
靶点

  • TGFβRI/ALK5

    ALK5, IC50:94 nM
描述 The TGF-β pathway regulates a wide variety of cellular processes in many different cell types and biological contexts. There are three identified TGF receptor ligands, TGF-β1, 2 and 3. Activated TGF-β ligands can interact with TGF-β type II receptors (TβRII), then recruit and phosphorylate the TGF-β type I receptors (also called as TβRI or ALK5). In turn, activated TβRI phosphorylates SMAD2 and SMAD3 at C-terminal serine residues. Following that, phosphorylated SMAD and SMAD3 assemble into heterodimeric and trimeric complexes with SMAD4. Then the trimeric complex translocate into the nucleus and regulate the expression of TGF-β target genes[3]. SB-431542 is a selective ALK5 inhibitor with IC50 value of 94nM (measured by GST-ALK5 kinase activity)[1]. SB-431542 also shows inhibition against ALK4 and ALK7, which are very similar to ALK5 in their kinase domains. Addition of SB-431542 for 24h at a concentration of 10uM can efficiently inhibit the p-Smad2 phosphorylated by activated ALK4, ALK5, and ALK7 in NIH 3T3 cells, with no effect on BMP induced phosphorylation of Smad1, which is mediated by ALKs 2, 3, and 6. The transcription activity mediated by the activated endogenous ALKs 4, 5 and 7 can also inhibited dose-dependently by 0.25, 0.5, 0.75, 1, 2, 5, or 10uM SB-431542[2]. SB-431542 has performance in both reprogramming and differentiation, as 1. SB-431542 can replace SOX2 in the reprogramming of mouse fibroblasts to iPSCs; 2. Combined with PD0325901 and Thiazovivin, SB-431542 can increase the efficiency of reprogramming human somatic cells to iPSCs; 3. SB-431542, combined with CHIR99021, ISX-9, Forskolin and I-BET151, can direct lineage reprogramming of fibroblasts to mature neurons; 4. SB-431542, in combination with either LDN193189 or Noggin, promotes the differentiation of NPCs from human PSCs; 5. SB-431542 can promote the proliferation and sheet formation of mouse ES-derived endothelial cells; 6. SB-431542 can enhance differentiation of cardiomyocytes.
作用机制 SB-431542 acts as a competitive ATP binding site kinase inhibitor[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
C32 10 μM Function Assay 20h Inhibits Trypanosoma cruzi Y infection-induced TGFbeta signaling in mink C32 cells at 10 uM 17526757
CHO-HIR 0.01-3 μM Function Assay 2 h Inhibits TGFbeta-induced downstream transcriptional activation of ALK5 expressed in CHO-HIR cells assessed as intracellular translocation of EGFP-Smad2 with IC50 of 0.35μM 24055046
H1299 1 μM Migration Assay 12-24 h Induces antimigratory activity against human H1299 cells assessed as Inhibition of cell migration with IC50 of 0.5μM 24417479
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.60mL

0.52mL

0.26mL

13.01mL

2.60mL

1.30mL

26.02mL

5.20mL

2.60mL
参考文献

[1]Callahan JF, Burgess JL, et al. Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem. 2002 Feb 28;45(5):999-1001.

[2]Halder SK, Beauchamp RD, et al. A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia. 2005 May;7(5):509-21.

[3]Colak S, Ten Dijke P, et al. Targeting TGF-β Signaling in Cancer. Trends Cancer. 2017 Jan;3(1):56-71.