SD-208

产品说明书

Print
Chemical Structure| 627536-09-8 同义名 : -
CAS号 : 627536-09-8
货号 : A150813
分子式 : C17H10ClFN6
纯度 : 99%
分子量 : 352.753
MDL号 : MFCD11519969
存储条件：

Pure form Keep in dark place,Inert atmosphere,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 8 mg/mL(22.68 mM)，配合低频超声助溶，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
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 1.3 mg/mL clear

PO 0.5% CMC-Na 47 mg/mL suspension

生物活性
靶点

  • TGFβRI/ALK5

    TGF-βRI (ALK5), IC50:48 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 translocates into the nucleus and regulates the expression of TGF-β target genes[2]. SD-208 is a selective inhibitor of TGF-βR1 with IC50 value of 48nM, 100-fold compared with TGF-βRII kinase (measured by cell-free kinase activity). Pre-exposure to 1uM SD-208 for 24h can abolish the p-Smad2 induced by 1-hour treatment of endogenous TGF-β or exogenous TGF-β (5ng/ml) in SMA-560 or LN-308 glioma cells. Decreased activity of TGF-β reporter, pGL2 3TP-Luc or pGL3 SBE-2 Luc reporter, can be observed in the presence of SD-208 at 0.1 or 1uM in the cells exposure to TGF-β (5ng/ml) for 16h. These results indicated the abrogation of TGF-β signaling by SD-208. SD-208, at 1uM for 24h, did not show direct cytotoxicity but can inhibit the migration and invasion of SMA-560 cells evoked by TGF-β (5ng/ml). Also, in vitro study showed SD-208 can enhance allogeneic immune responses to glioma cells. Orally administered SD-208 on dose of 30, 90 and 120mg/kg can inhibit TGF-β–dependent phosphorylation of Smad2/3 in brain of SMA-560 intracranial experimental glioma-bearing syngeneic mice, as well as prolonged the survival of the mice[1]. SD-208 at concentration of 30-300nM for 48h can abrogate IL-6 and VEGF secretion from BMSCs cultured with MM cells, as well as SD-208 abrogates IL-6 and VEGF secretion from BMSCs cultured with MM cells, which showed the regulation activity of SD-208 on MM cells in the bone marrow microenvironment[3]. Inhibition of TGF-β signaling by SD-208 can inhibit the induction of fibrosis and block progressive fibrosis in pulmonary fibrosis rat models[4].
作用机制 SD-208 is an ATP–competitive ALK5 inhibitor.[5]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.83mL

0.57mL

0.28mL

14.17mL

2.83mL

1.42mL

28.35mL

5.67mL

2.83mL
参考文献

[1]Uhl M, Aulwurm S, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61.

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

[3]Hayashi T, Hideshima T, et al. Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. Clin Cancer Res. 2004 Nov 15;10(22):7540-6.

[4]Bonniaud P, Margetts PJ, et al. Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am J Respir Crit Care Med. 2005 Apr 15;171(8):889-98. Epub 2004 Nov 24.

[5]Huynh QK, Wise SJ, et al. Screening and identification of a novel class of TGF-β type 1 receptor kinase inhibitor. J Biomol Screen. 2011 Aug;16(7):724-33.