ex 527

Selisistat (EX-527) is a potent and specific inhibitor of the deacetylase SIRT1 (IC50 = 38 nM) and can be utilized in the study of neurological disorders such as Huntington's chorea.

Selisistat S-enantiomer (EX-527 S-enantiomer) is an effective and specific SIRT1 inhibitor (IC50 = 98 nM) and shows >200-fold selectivity against SIRT2 3.

Selisistat R-enantiomer (EX-527 (R-enantiomer)) is a SIRT1 inhibitor with much less activity than the R-enantiomer of Selisistat (IC50 of SIRT1 > 100 μM).

PKSI-527 is an inhibitor of plasma kallikrein (Ki = 0.81 μM). It is selective for plasma kallikrein over glandular kallikrein, plasmin, thrombin, urokinase, and Factor Xa (Kis = >500, 390, >500, 200, and >500 μM, respectively). PKSI-527 reduces bradykinin generation induced by kaolin and λ-carrageenan ex vivo in human plasma. It also prolongs partial thromboplastin and euglobulin clot lysis times. In vivo, PKSI-527 (300 mg/kg per day) reduces hyperplasia, pannus formation, and infiltration of inflammatory cells in the tarsal joint of mice with collagen-induced arthritis.