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RepSox (E-616452 or SJN 2511) is a highly potent, selective inhibitor of the TGF-β type I receptor ALK5 with IC₅₀ of 23 nM and 4 nM for ATP binding to ALK5 and ALK5 autophosphorylation, respectively. It has good selectivity for ALK5 over a range of kinases, including p38 MAPK, JNK1 and GSK3 (IC₅₀ > 16 μM). RepSox is able to successfully replace Sox2 in reprogramming by inhibiting transforming growth factor-β (Tgf-β) signaling, which in turn induces Nanog expression. Effect of RepSox inducing reprogramming does not require chromatin remodeling. RepSox is found to be efficient at generating iPSCs.

How to Use:

• In vitro: RepSox was used at 1-25 μM final concentration in vitro and in stem cell reprogramming.
• In vivo: RepSox is able to be contribute to forming chimeric embryos in vivo when injected into blastocysts. A one-day treatment with RepSox is sufficient to replace transgenic Sox2.

Reference:

1. 1. Gellibert F, et al. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. (2004) J Med Chem. 47(18):4494-506.
2. 2. Ichida JK, et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. (2009) Cell Stem Cell. 5(5):491-503.
3. 3. Li W, et al. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. (2009) Cell Stem Cell. 4(1):16-9.
4. 4. Liu X, et al. Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. (2013) Nat Cell Biol. 15(7):829-38.
5. 5. Hou P, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. (2013) Science. 341(6146):651-4.

Products are for research use only. Not for human use.