Description
RepSox (446859-33-2) is a potent (IC50?ALK5 auto-P= 4 nM; IC50?TGF-β cellular assay = 23 nM) inhibitor of the TGF-β type I receptor (ALK5).1?RepSox can replace Sox2 in reprogramming adult cells into pluripotent stem cells via induction of Nanog transcription.2?It was able to convert astrocytes into neuronal cells as part of a small molecule cocktail (along with valproic acid and CHIR99021).3,4
Uses
Alk 5 Inhibitor II is a selective ATP competitive inhibitor of transforming growth factor-β (TGFβ). A potential drug for the treatment of fibrosis and cancer.
Definition
ChEBI: 1,5-naphthyridine, 2-[3-(6-methyl-2-pyridinyl)-1h-pyrazol-4-yl]- is a pyrazolopyridine.
Biological Activity
Cell permeable, potent, selective and ATP-competitive inhibitor of TGF-β RI kinase (IC50=23nM, 4nM and 18nM for binding, auto-phosphorylation and cellular assay in HepG2 cells of TGF-β RI kinase, respectively). Minimally affects a panel of 9 closely related kinases including p38 MAPK (IC50>16μM).
Biochem/physiol Actions
RepSox Inhibits TGF-beta receptor signaling. Retroviral transduction of Sox2, Oct4, and Klf4 genes results in direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs).
References
1) Gellibert?et al. (2004),?Identification of 1,5-Naphthyridine Derivatives as a Novel Series of Potent and Selective TGF-β Type I Receptor Inhibitors; J. Med. Chem.?47?4494
2) Ichida?et al.?(2009),?A Small-molecule Inhibitor of TGF-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog; Cell Stem Cell?5?491
3) Cheng?et al.?(2015),?Direct Conversion of astrocytes into neuronal cells by a drug cocktail;?Cell Res.?25?1269
4) Cheng?et al.?(2014),?Generation of neural progenitor cells by chemical cocktails and hypoxia; Cell Res.?24?665
