ML133 HCl selectively inhibit Kir2.1 with IC50 of 1.8 μM at pH7.4 and 290 nM at pH8.5 and has no effect on Kir1.1 and weak activity for Kir4.1 and Kir7.1.
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ML133 hydrochloride is a selective Kir2 family channels inhibitor, with an IC50 of 1.8 μM at pH 7.4 and 290 nM at pH 8.5, but exhibits little selectivity against other members of Kir2.x family channels. ML133 has no effect on Kir1.1 (IC50 > 300 μM), and displays weak activity for Kir4.1 (76 μM) and Kir7.1 (33 μM), making ML133 the most selective small molecule inhibitor of the Kir family reported to date[3]. Transplantation of ML133-treated or Kir2.1 knockdown EPCs (Endothelial progenitor cells) facilitated re-endothelialization in the rat injured arterial segment and inhibited neointima formation in vivo. In parallel, ML133 significantly enhanced autophagy and autophagic flux. After suppression of autophagy by 3-methyladenine (3-MA), the effects of ML133 on in vitro function and in vivo endothelialization capacity of EPCs were significantly inhibited[4].
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