StemRegenin 1 (SR1)
Molecular Weight(MW): 429.54
StemRegenin 1 is an aryl hydrocarbon receptor (AhR) inhibitor with IC50 of 127 nM in a cell-free assay.
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|Description||StemRegenin 1 is an aryl hydrocarbon receptor (AhR) inhibitor with IC50 of 127 nM in a cell-free assay.|
StemRegenin 1 increases the number of CD34+ cells after 5 to 7 days with an EC50 of 120 nM. Culture of mPB CD34+ cells with cytokines plus SR1 (1 μM) for 7 days increases the number of CD34+, CD133+, and CD90+ hematopoietic stem and progenitor cell populations 2.6-, 2.3-, and 10-fold, respectively compared to control cells. Continued culture with SR1 (1 μM) for 3 weeks leads to an 11-fold increase in total nucleated cells (TNC), a 73-fold increase in CD34+ cells as compared to control cultures, and a 1118-fold increase in CD34+ cells relative to input cells. Culture of 1×103 cord blood CD34+ cells for 5 weeks with SR1 (1 μM) results in the production of 1.69×106 colony forming cells. SR1-induces CD34+ cell expansion acts by binding and antagonizing AhR as evident by decreased CYP1B1 and AHRR mRNA levels.  SR1 (1 μM) treatment accelerates the proliferation of CD34+ cells and decreased the expression levels of VentX in human CD34+ cells. Ectopic expression of VentX prevents SR1-induced expansion of CD34+ cells.  Sequential coculture with bone morphogenetic protein 4 (20 ng/mL), PGE2 (2 μM), and SR1 (0.75 μM) lead to robust Macaca nemestrina iPSC hematopoietic progenitor cell formation. CD34(+)CD38(-)Thy1(+)CD45RA(-)CD49f(+) cells isolated on the basis of CD34 expression and cultured in SR1 (0.75 μM) expands 3-fold and maintained this long-term repopulating HSC phenotype. 
|In vivo||SR1 promotes expansion of CB CD34+ cells that contribute to both early and sustained engraftment NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. |
|In vitro||DMSO||86 mg/mL (200.21 mM)|
* 1 mg/ml means slightly soluble or insoluble.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02827513||Terminated||Adult Attention-deficit Hyperactivity Disorder (ADHD)||Neurovance, Inc.|Euthymics BioScience, Inc.||December 2015||Phase 1|
|NCT01744808||Completed||Normal, Healthy Volunteers||Neurovance, Inc.|Euthymics BioScience, Inc.||February 2013||Phase 1|
|NCT00557973||Completed||Muscle Spasticity||Indivior Inc.||December 2007||Phase 2|
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