StemRegenin 1 (SR1)

StemRegenin 1 is a potent aryl hydrocarbon receptor (AhR) antagonist with IC50 of 127 nM.

Signaling Pathways >> Immunology/Inflammation >> Aryl Hydrocarbon Receptor

Research Areas >> Cancer

IC50: 127 nM (AhR)[1]

StemRegenin 1 (SR1) acts by antagonizing the aryl hydrocarbon receptor (AhR). StemRegenin 1 increases the number of CD34+ cells after 5 to 7 days with an EC50 of ~120 nM. StemRegenin 1 inhibits photoaffinity ligand (PAL) binding (IC50=40 nM) These results support the conclusion that StemRegenin 1 -induced CD34+ cell expansion is mediated through direct binding and inhibition of the AhR[1]. An aryl hydrocarbon receptor antagonist, StemRegenin 1 (SR1), robustly promotes ex vivo expansion of human CD34+ cells. StemRegenin 1 treatment accelerates the proliferation of CD34+ cells and decreases the expression levels of VentX[2].

A quantity of 250,000 CB-derived CD34+ cells are cultured with control conditions (DMSO, 0.01%) or StemRegenin 1 (0.75 μM) for 3 weeks. At this point control cultures had expanded 1080-fold and StemRegenin 1 treated cells expanded 2024-fold relative to starting cell numbers. A quantity of 30 to 30,000 uncultured CD34+ CB-derived cells or a fraction of the final culture equivalent to 30 to 10,000 starting cells are transplanted. The cells are injected intravenously via the retro-orbital route into sub-lethally irradiated (300 rads, 200 rads) 6- to 10-week-old NSG mice. Engraftment is performed within 24 h after irradiation. Engraftment is monitored by flow cytometric analysis of blood obtained via retro-orbital sinus or bone marrow using anti-human CD45 and anti-mouse CD45 antibodies. The mice are sacrificed between 13-16 weeks posttransplantation; bone marrow (from both femurs and tibiae), spleen and thymus are collected for analysis. For secondary engraftment, 50% of the bone marrow from each recipient mouse is transplanted into one secondary sub-lethally irradiated NSG mouse. Fifteen weeks after transplantation, bone marrow is harvested from the secondary mice and analyzed by flow cytometry[1].

[1]. Boitano AE, et al. Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells. Science. 2010 Sep 10;329(5997):1345-8.

[2]. Gao H, et al. Suppression of homeobox transcription factor VentX promotes expansion of human hematopoietic stem/multipotent progenitor cells. J Biol Chem. 2012 Aug 24;287(35):29979-87.

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