SD-208

Catalog No.S7624

SD-208 Chemical Structure

Molecular Weight(MW): 352.75

SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.

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Biological Activity

Description SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.
Targets
TGF-βRI (ALK5) [1]
(Cell-free assay)
48 nM
In vitro

SD-208 inhibits the cell growth and constitutive and TGF-beta-evoked migration and invasion, and enhances immunogenicity in murine SMA-560 and human LN-308 glioma cells. [1] SD-208 blocka TGF-beta-induced phosphorylation of the receptor-associated Smads, Smad2 and Smad3, and stimulates epithelial-to-mesenchymal transdifferentiation, migration, and invasiveness into Matrigel in vitro. [2] SD-208 also abolishes the promoting effect of TGF-β on neointimal smooth muscle-like cell (SMLC) proliferation and migration in vitro. [3]

In vivo SD-208 (1 mg/mL, p.o.) significantly prolongs the median survival of SMA-560 glioma-bearing mice. [1] In syngeneic 129S1 mice, SD-208 (60 mg/kg/d, p.o.) inhibits primary R3T tumor growth, and reduces the number and the size of lung metastases. [2] In the murine aortic allograft model, SD-208 effectively reduces the formation of intimal hyperplasia of transplant arteriosclerosis (TA). [3]

Protocol

Kinase Assay:[1]
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Kinase assay:

Various kinase activities are assayed by measuring the incorporation of radiolabeled ATP into a peptide or protein substrate. The reactions are performed in 96-well plates and included the relevant kinase, substrate, ATP, and appropriate cofactors. The reactions are incubated and then stopped by the addition of phosphoric acid. Substrate is captured onto a phosphocellulose filter, which is washed free of unreacted ATP. The counts incorporated are determined by counting on a microplate scintillation counter. The ability of SD-208 to inhibit the respective kinase is determined by comparing counts incorporated in the presence of compound with those incorporated in the absence of compound.
Cell Research:[1]
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  • Cell lines: Murine SMA-560 and human LN-308 glioma cells
  • Concentrations: 1 μM
  • Incubation Time: 48 hours
  • Method: Glioma cells are cultured in the absence or presence of SD-208 (1 μM) for 48 hours. The cells are pulsed for the last 24 hours with [methyl-3H]thymidine (0.5 μCi) and harvested, and incorporated radioactivity is determined in a liquid scintillation counter.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: VM/Dk mice bearing SMA-560 tumors
  • Formulation: deionized water
  • Dosages: 1 mg/mL
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 9 mg/mL warmed (25.51 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% methylcellulose
8mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 352.75
Formula

C17H10ClFN6

CAS No. 627536-09-8
Storage powder
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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TGF-beta/Smad Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID