BI-9627

BI-9627, a chemical probe, is a potent sodium-hydrogen exchanger isoform 1 (NHE1) inhibitor (IC₅₀ = 6 and 31 nM in intracellular pH recovery (pH_i) and human platelet swelling assays). BI-9627 displays >30-fold selectivity against NHE2 and with no measurable inhibitory activity against the NHE3 isoform. BI-9627 decreases autophagy in HTR-8/SVneo cells. BI-9627 can significantly reduce the pH_i of human sperm and partially reverse the effect of DMA. BI-9627 prolongs Ca²⁺ recovery time in KO hiPSC-CMs. BI-9627 shows low DDI (agent-agent interaction) potential, excellent pharmacokinetics in rat and dog, and remarkably potent activity in the isolated heart model of ischemia-reperfusion injury^[1][2][3][4]. IC50 & Target:IC50: 6 nM (NHE1 in intracellular pH recovery assay), 31 nM (NHE1 in human platelet swelling assay)^[1] In Vitro:BI-9627 (Compound 60) exhibits the most potent inhibition of NHE1 among all tested compounds with IC₅₀ of 6 and 31 nM in pH_i assay and platelet swelling assay^[1].
BI-9627 (10-100 nM, 0-80 min) provides a significantly beneficial effect on left-ventricular end diastolic pressure, preventing much of the increase seen postreperfusion for the vehicle control in the Langendorff isolated perfused rat heart model^[1].
BI-9627 (50 nM, 2 h) leads to a significant decrease in LC3-II/I ratio in HTR-8/SVneo cells as well as human trophoblast cells, suggesting a decrease in autophagy^[2].
BI-9627 (100 nM, 24 h) reverses the abnormalities in Ca²⁺-transient-related parameters in KO hiPSC-CMs^[4].
BI-9627 (100 nM, 7 d) elevates diastolic Ca²⁺ levels and prolongs Ca²⁺ recovery time in KO hiPSC-CMs^[4]. In Vivo:BI-9627 shows low DDI (agent-agent interaction) potential, excellent pharmacokinetics in rat and dog, and remarkably potent activity in the isolated heart model of ischemia-reperfusion injury^[1].