Fig. 1.

Identification and structure-based optimization of a potent and selective FB inhibitor. (A) Chemical structure of compound 1, compound 2, and LNP023 and corresponding IC₅₀ values for inhibition of FB. (B) Cocrystal structure of human FB in complex with compound 1 (yellow sticks) at 1.64 Å resolution. (C) Overlay of compound 1 (yellow sticks) and compound 2 (white sticks) with close-up view into the S1 pocket. (D) Overlay of compound 2 (white sticks) and LNP023 (cyan sticks). A sulfate ion (yellow) from the cocrystal structure of compound 2 is shown. The catalytic residues His57 and Ser195 and other key residues of the ligand binding pockets are highlighted and shown as sticks.