StemRegenin 1 (hydrochloride)

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Background

IC50: 127 nM in CD34+ cellsStemRegenin 1 is an aryl hydrocarbon receptor signaling antagonist.The aryl hydrocarbon receptor (AhR ) is a protein that is encoded by the AHR gene. The AhR is a ligand-activated transcription factor involved in the regulation of biological responses to planar aromatic (aryl) hydrocarbons. In vitro: In previous study, the unbiased screen with primary human HSCs identified the StemRegenin 1 (SR1), which could promote the ex-vivo expansion of CD34+ cells. In addition, the culture of HSCs with SR1 resulted in a 50-fold increase in cells expressing CD34. Moreover, the mechanistic studies showed that SR1 acted by antagonizing the AhR [1]. In vivo: In aninmal study, 300 to 30,000 uncultured CB CD34+ cells were transplanted into NSG mice. Results showed that CB CD34+ cells cultured with SR1 led to significant increases in human engraftment in the peripheral blood at 1 week, compared with mice transplanted with 10,000 uncultured cells or the progeny of 10,000 control cells [1]. Clinical trial: An open label, randomized phase II trial comparing SR-1 cultured umbilical cord blood to unmanipulated umbilical cord blood transplantation after a myeloablative CY/FLU/TBI conditioning has been proposed, but is not yet open for participant recruitment [2].

[1] A. E. Boitano, J. Wang, R. Romeo, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 329,1345-1348 (2010).
[2] https://clinicaltrials. gov/ct2/show/NCT02765997 term=StemRegenin+1&rank=1