ASP-8731 is an orally active BACH1 inhibitor. ASP-8731 activates antioxidant, anti-inflammatory and globin gene pathways by relieving the inhibitory effect of BACH1 on NRF2-mediated gene transcription. ASP-8731 significantly upregulates the expression of HMOX1, FTH1 and various globins (such as HGB, HBG, HBA), increases fetal hemoglobin (HbF) levels, and effectively induces F-cell production in hydroxyurea-unresponsive cells. Meanwhile, ASP-8731 reduces inflammatory responses and white blood cell counts by downregulating VCAM1, ICAM-1 and the phosphorylation level of NF-kappaB(p65), and blocks heme-induced glutathione depletion and microcirculatory stasis. ASP-8731 holds potential for inhibiting sickle cell disease and related hematological disorders[1].
