HI-6

**HI-6** is a bispyridinium oxime compound developed as a cholinesterase reactivator and antidote for organophosphate (OP) nerve agent poisoning, particularly effective against soman, sarin, VX, and cyclosarin-inhibited acetylcholinesterase (AChE). It functions by reactivating OP-inhibited AChE through nucleophilic attack at the phosphorylated serine residue in the enzyme's active site, displacing the inhibitor and restoring enzymatic activity; structural studies show its oxime-pyridinium ring entering the catalytic site with cation-pi interactions to residues like Tyr124, Tyr337, and hydrogen bonding networks aiding deprotonation for reactivation.[1][2][3][4] Primarily an experimental therapeutic without widespread commercial approval, it has been investigated in liposomal formulations (e.g., PEGylated liposomes) to improve pharmacokinetics, prolong plasma residence, and enhance brain delivery for on-site first-aid in acute OP poisoning.[5]

Other names

1-[[[4-(Aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]-pyridinium chloride4-Carbamoyl-1-[[[2-[(hydroxyimino)methyl]pyridinium-1-yl]methoxy]methyl]pyridinium dichlorideAsoxime chloride