VK-II-86

VK-II-86 is an inhibitor of store-overload-induced calcium release (SOICR) and a derivative of carvedilol (Cay-15418). It inhibits SOICR in HEK293 cells expressing the ryanodine receptor 2 (RyR2) R4496C (RyR2R4496C) mutation (IC50 = 16.8 µM), a mutation that results in spontaneous calcium release from the endoplasmic reticulum. VK-II-86 (1 µM) inhibits the inward-rectifier potassium channel 2.1 (Kir2.1), cardiac late sodium current (late INa), and L-type calcium current (ICa) in isolated canine cardiomyocytes and delayed-rectifier potassium current (IKr) in HEK293 cells expressing human-ether-a-go-go (hERG), also known as Kv11.1, in hypokalaemic, but not normokalaemic, conditions. It is also an antagonist of toll-like receptor 4 (TLR4, IC50 = 32.55 µM in HEK293 cells expressing the human receptor) and inhibits hyperpolarization-activated cyclic nucleotide gated potassium channel 4 (HCN4) in COS-7 cells expressing HCN4 when used at a concentration of 10 µM. VK-II-86 prevents hypokalaemia-induced ventricular arrhythmia in isolated Langendorff-perfused mouse hearts. Unlike the beta-adrenergic receptor antagonist carvedilol, it does not reverse isoproterenol-induced increases in heart rate or decrease resting heart rate in RyR2R4496C-expressing mice.Formal Name: 4-(9H-carbazol-4-yloxy)-1-[[2-(2-methoxyphenoxy)ethyl]amino]-2-butanol. CAS Number: 955371-84-3. Molecular Formula: C25H28N2O4. Formula Weight: 420.5. Purity: >90%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. lambdamax: 244 nm. SMILES: OC(CCOC1=CC=CC2=C1C3=C(C=CC=C3)N2)CNCCOC4=C(OC)C=CC=C4. InChi Code: InChI=1S/C25H28N2O4/c1-29-22-10-4-5-11-23(22)31-16-14-26-17-18(28)13-15-30-24-12-6-9-21-25(24)19-7-2-3-8-20(19)27-21/h2-12,18,26-28H,13-17H2,1H3. InChi Key: OHYHNEODRHJYSS-UHFFFAOYSA-N.