SB-431542 is a potent and selective inhibitor of ALK5 (IC50: 94 nM) and is also an inhibitor of ALK4 (IC50: 140 nM) and ALK7.

SB-431542 inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay [1]. SB-431542 (1 μM) significantly reduced the TGFβ–induced nuclear accumulation of Smad proteins. The IC50 for inhibiting TGFβ–induced nuclear fluorescence is approximately 50 nM. BMP-stimulated Smad1 nuclear fluorescence in MG63 cells was unaffected by SB-431542 [2]. the synergistic action of two inhibitors of SMAD signaling, Noggin and SB431542, is sufficient to induce rapid and complete neural conversion of >80% of hES cells under adherent culture conditions [3].

SB-431542 augmented the capacity of bone marrow dendritic cells (BM-DCs) and human DCs to incorporate FITC-conjugated dextran. Intraperitoneal administration of SB-431542 initiated 3 and 7 days after the implantation of colon-26 cancer cells into the peritoneal cavity of BALB/c mice significantly induced CTL activity against colon-26 [4]. SB-431542 significantly inhibited lung metastasis from transplanted 4T1 mammary tumors in Balb/c mice [5].

Kinase assays were performed with 65 nM GSTALK5 and 184 nM GST-Smad3 in 50 mM HEPES, 5 mM MgCl2, 1 mM CaCl2, 1 mM dithiothreitol, and 3 M ATP. Reactions were incubated with 0.5 μCi of [33P]γATP for 3 h at 30°C. Phosphorylated protein was captured on P-81 paper, washed with 0.5% phosphoric acid, and counted by liquid scintillation. Alternatively, Smad3 or Smad1 protein was also coated onto FlashPlate Sterile Basic Microplates. Kinase assays were then performed in FlashPlates with same assay conditions using either the kinase domain of ALK5 with Smad3 as a substrate or the kinase domain of ALK6 (BMP receptor) with Smad1 as substrate. Plates were washed three times with phosphate buffer and counted by TopCount [2].

A498 cells were seeded at 5,000 to 10,000 cells/well in 96-well plates. The cells were serum-deprived for 24 h and then treated with compounds for 48 h to assess the cellular toxicity. Cell viability is determined by incubating cells for 4 h with XTT labeling and electron coupling reagent. Live cells with active mitochondria produce an orange-colored product, formazan, which is detected using a plate reader at between A450 nm and A500 nm with a reference wavelength greater than 600 nm. The absorbance values correlate with the number of viable cells [2].

BALB/c mice received intraperitoneal (i.p.) injections of colon-26 tumor cells. Three days after tumor cell inoculation, SB-431542 (1 μM solution, 100 μl/animal) or vehicle alone was directly injected into the peritoneal cavity. CTL activities were measured by a standard 4 h 51Cr release assay after culturing spleen cells with γ-irradiated tumor cells for five days in the absence of added growth factors. In vitro experiments, cell lysate of HLA-A*2402 positive gastric cancer cell line, OCUM-8, was incubated with human DC cultures for 4 h. After washing extensively, PBMCs obtained from the same volunteer as DCs were incubated for 7 days and measured CTL activity by 51Cr release assay. NK activity was tested using 51Cr release assay against K562 [4].

301836-41-9

C22H16N4O3

384.395

4-[4-(1,3-苯并二唑-5-基)-5-(2-吡啶基)-1H-咪唑-2-基]-苯酰胺水合物;SB 431542;SB-431542

[1]Ma J, et al. Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion. Brain Res Bull. 2018 Feb 9;139:38-47. [2]Laping NJ, et al. Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542. Mol Pharmacol. 2002 Jul;62(1):58-64. [3]Duan F, Huang R, Zhang F, et al. Biphasic modulation of insulin signaling enables highly efficient hematopoietic differentiation from human pluripotent stem cells[J]. Stem cell research & therapy. 2018 Jul 27;9(1):205. [4]Callahan JF, 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. [5]Chen F, Gao Q, Wei A, et al. Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis[J]. Cell Death & Differentiation. 2020: 1-12. [6]Chambers SM, et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009 Mar;27(3):275-80. [7]Tanaka H, et al. Transforming growth factor β signaling inhibitor, SB-431542, induces maturation of dendritic cells and enhances anti-tumor activity. Oncol Rep. 2010 Dec;24(6):1637-43. [8]Xiong, Yanlu, et al. TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway. . Cell Death & Disease . 12.4 (2021): 1-13. [9]Sato M, et al. Differential Proteome Analysis Identifies TGF-β-Related Pro-Metastatic Proteins in a 4T1 Murine Breast Cancer Model. PLoS One. 2015 May 18;10(5):e0126483.

[1]Chen X, Wang P, Qiu H, et al. Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction. Nature Communications. 2022, 13(1): 1-16 [2]Duan F, Huang R, Zhang F, et al. Biphasic modulation of insulin signaling enables highly efficient hematopoietic differentiation from human pluripotent stem cells. Stem Cell Research & Therapy. 2018 Jul 27;9(1):205 [3]Bao, Shixiang, et al. TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma. Frontiers in Oncology. 11 (2021): 2516. [4]Bao, Shixiang, et al. TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma. Frontiers in Oncology. 11 (2021): 2516. [5]Bao, Shixiang, et al. TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma. Frontiers in Oncology. 11 (2021): 2516. [6]Fu J, Jiang L, Yu B, et al. Generation of a Human iPSC Line CIBi010-A with a Reporter for ASGR1 Using CRISPR/Cas9. Stem Cell Research. 2022: 102800

Ethanol:3.8 mg/mL (10 mM)
DMSO:38.4 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years