LYS006 (LY-S006) is a potent, highly selective leukotriene A4 hydrolase (LTA4H) inhibitor with biochemical IC50 of 0.12 nM.
LYS006 demonstrates high potency (IC50=53 nM) in human whole blood ionophore-stimulated LTB4 release assay.
LYS006 shows an exquisite selectivity profile at 10 uM on a panel of >150 GPCRs, transporters, ion channels, nuclear receptors, and enzymes in vitro, does not inhibit other Zn2+ containing MMPs including MMP1, 2, 8, 9, 12, 13, 14 and TACE at 30 uM. LYS006 dependently inhibited ex vivo LTB4 formation, inhibited LTB4 production by 90% at dose >1 mg/kg, reduced MPO in skin homogenates y in neutrophilic skin inflammation models.
LYS006 (0.1-3 mg/kg) suppressed neutrophilic inflammation in arachidonic acid induced skin inflammation model.
LYS006 has the potential for a best-in-class LTA4H inhibitor and is currently investigated in phase II clinical trials in inflammatory acne, hidradenitis suppurativa, ulcerative colitis, and NASH.