化合物 SID 26681509 QUARTERHYDRATE

IC50: 56 nM (Human cathepsin L), 0.5 μM (Cathepsin V), 15.4 μM ( Plasmodium falciparum ), 12.5 μM ( Leishmania major )

After a 4 hr preincubation with cathepsin L, SID 26681509 becomes more potent, demonstrating an IC ₅₀ of 1.0 nM. SID 26681509 is determined to be a slow-binding and slowly reversible competitive inhibitor. Through a transient kinetic analysis for single-step reversibility, inhibition rate constants are kon = 24,000 M ^-1 s ^-1 and koff = 2.2 × 10 ^-5 s ^-1 (K _i = 0.89 nM). Molecular docking studies are undertaken using the experimentally-derived X-ray crystal structure of papain/CLIK-148.
SID 26681509 inhibits papain and cathepsins B, K, S, and V with IC ₅₀ values determined after one hour ranging from 618 nM to 8.442 μM. SID 26681509 shows no inhibitory activity against the serine protease cathepsin G.
SID 26681509 inhibits cathepsin V activity with an IC ₅₀ value of 0.5 μM. SID 26681509 (1-30 μM) blocks high-mobility group box 1 (HMGB1)-induced TNF-α production dose dependently without altering cell viability.

SID 26681509 treatment significantly improves survival in murine models of sepsis and reduces liver damage following warm liver ischemia/reperfusion (I/R) models.