RepSox is a small molecule inhibitor of TGFβR1,[1][2] also known as ALK5, that was first identified in the wake of the discovery of the Yamanaka factors.[3] It has shown promise in a variety of in-vitro and in-vivo rodent trials modelling various diseases. It inhibits TGFβR1 autophosphorylation by preventing the protein from binding with ATP, inhibits the binding of TGF-β to TGFβR1, and prevents the transcription of genes activated by TGFβR1 with nanomolar potency.[4] RepSox is a member of the 1,5-naphthyridine class.
RepSox suppresses the proliferation of osteosarcoma cells via suppression of the JNK/Smad3 signalling pathway, and was able to induce cell cycle arrest, promote apoptosis and prevent migration of the cancer cells. The results were replicated both in-vitro and in-vivo.[7]
RepSox was able to promote the transformation of glial cells to neurons in the enteric nervous system of adult mice, consequently influencing gastrointestinal motility, and underlining a potential therapeutic use of RepSox in enteric neuropathies.[8]
History
RepSox was discovered by a team at the Harvard Stem Cell Institute looking for way to induce pluripotency without inserting the gene Sox2 into cells. They discovered a molecule which was capable of this but also was able to reprogram cells in the absence of c-Myc, a tumour promoting gene. They named the molecule RepSox since it can replace Sox2 and in homage to the Boston Red Sox.[3]
