RepSox

RepSox

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: unscheduled
Identifiers
IUPAC name 2-[5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine
CAS Number	446859-33-2 Y
PubChem CID	449054
ChemSpider	395681
UNII	JT8ZW3H2ST
ChEBI	CHEBI:190969
ChEMBL	ChEMBL185238
CompTox Dashboard (EPA)	DTXSID80332295
ECHA InfoCard	100.190.188
Chemical and physical data
Formula	C17H13N5
Molar mass	287.326 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NC(=CC=C1)C2=C(C=NN2)C3=NC4=C(C=C3)N=CC=C4
InChI InChI=InChI=1S/C17H13N5/c1-11-4-2-5-16(20-11)17-12(10-19-22-17)13-7-8-14-15(21-13)6-3-9-18-14/h2-10H,1H3,(H,19,22) Key:LBPKYPYHDKKRFS-UHFFFAOYSA-N

RepSox is a small molecule inhibitor of TGFβR1, also known as ALK5, that was first identified in the wake of the discovery of the Yamanaka factors. 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. RepSox is a member of the 1,5-naphthyridine class.

Research

In an in-vivo trial of rats with ovariectomy-induced osteoporosis, RepSox was shown to prevent bone loss. RepSox is included as a part of some chemical cocktails intended for cellular reprogramming and anti-aging, where it works by inducing the expression of the gene Nanog.

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.

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.

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.