A selective inhibitor of ALK5
RepSox is a potent and selective inhibitor of the TGFβR-1 with IC50 of 23 nM [1].
TGFβR-1 belongs to the TGFβ receptor family, which is a serine/threonine kinase receptor and bind ligand TGFβ. It gets involved in tumor transformation, cell differentiation and proliferation.
RepSox was found to replace the function of Sox2 to induce reprogramming of iPS cells, via the mechanism of inhibiting TGFβR-1 [1]. MEF cells were treated with RepSox for 3 days, and then it was removed at the time of transduction with Oct4, Klf4, and cMyc. The result showed the TGFβR-1 -associated expression of L-Myc was increased by 5-fold after RepSox treatment [1]. A partially reprogrammed cell line (OKMS 6) was treated with RepSox and performed global gene expression analysis at 10, 24, and 48 hours following the initiation of treatment. The result showed the Id1, Id2 and Id3 gene, repressed by TGFβR-1 signaling, were released from that repression and the expression level was increased. Additionally, other genes responsive for TGFβR-1 signaling were inhibited. It suggested RepSox was able to inhibit TGFβR-1 and suppress the TGFβR-1 downstream signaling [1].
In mouse model, iPS cells reprogrammed by RepSox were labeled with Tomato-red protein and then they were injected mouse blastocysts to produce mosaic embryo. The result showed that both embryo and adult mouse were with significant contribution from RepSox induced iPS cells. It suggested that the inhibitory activity of RepSox for TGFβR-1 was active in vivo [1].
Reference:
[1] Ichida J K et al.?, A small molecule inhibitor of Tgaf-β signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell, 2009, 5(5): 491-503.
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Cell lines |
MEFs |
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Preparation method |
The solubility of this compound in DMSO is > 14.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
25 μ M; 3 days |
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Applications |
In MEFs pretreated with RepSox, which were then transfected with Oct4, Klf4 and cMyc, there was no Oct4::GFP+ colony formed. The result showed the TGFβR-1-associated expression of L-Myc was increased by 5-fold after RepSox treatment. |
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参考文献: [1]. Ichida J K et al. , A small molecule inhibitor of Tgaf-β signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell, 2009, 5(5): 491-503. |
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