product name SD-208
Description: SD-208, also known as TGF-β RI Kinase Inhibitor V, is a novel, selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, it displayed >100-fold selectivity over TGF-βRII. SD-208 blocks prostate cancer cell proliferation and tumor growth in vivo by inducing G2/M cell cycle arrest. SD-208 reduces the development and progression of melanoma bone metastases. SD-208 inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo.
References: Cancer Res. 2004 Nov 1;64(21):7954-61; Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4315-30.
352.75
Formula
C17H10ClFN6
CAS No.
627536-09-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 9 mg/mL (25.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% methylcellulose: 8 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. 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. SD-208 also abolishes the promoting effect of TGF-β on neointimal smooth muscle-like cell (SMLC) proliferation and migration in vitro. 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 Assay: 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. |
|---|---|
| In Vivo | SD-208 (1 mg/mL, p.o.) significantly prolongs the median survival of SMA-560 glioma-bearing mice. 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. In the murine aortic allograft model, SD-208 effectively reduces the formation of intimal hyperplasia of transplant arteriosclerosis (TA). |
| Animal model | VM/Dk mice bearing SMA-560 tumors |
| Formulation & Dosage | Dissolved in water; 1 mg/mL; p.o. |
| References | Cancer Res. 2004 Nov 1;64(21):7954-61; Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4315-30. |
