Background:
UM729 is a small molecule enhancer of AhR antagonists [1].
UM729 has been found to be a new pyrimidoindole and have an additive efficacy with AhR antagonists in preventing differentiation in most AML specimen. In addition, UM729 has been reported to expand mormal HSPCs in a AhR-independent fashion. Moreover, UM729 has shown an additive effect with AhR inhibitors(SR1) on the ex vivo culture of primary human AML cells（05H163 cells） and progenitor cells [1]. Besides, UM729 has been revealed to expand HSCs and synergize with SR1 to enhance human HSC expansion, result in successful long-term engraftment of SCID repopulating cells (SRCs) in immunodeficient mice [2].
参考文献:
[1] Pabst C1, Krosl J1, Fares I1, Boucher G1, Ruel R1, Marinier A2, Lemieux S3, Hébert J4, Sauvageau G4.Identification of small molecules that support human leukemia stem cell activity ex vivo. Nat Methods. 2014 Apr;11(4):436-42.
[2] Watts K L, Chandrasekaran D, Sauvageau G, et al. Effective Expansion and Engraftment Of Nonhuman Primate CD34+ Hematopoietic Stem Cells After Co-Culture With The Small Molecule UM171[J]. Blood, 2013, 122(21): 1656-1656.
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