BI 1015550 (Nerandomilast, VRN024219) is a potent, selective PDE4B inhibitor that preferentially inhibits hydrolysis of cAMP by PDE4B with IC50 of 10 nM, weakly inhibits PDE4A/4C/4D (IC50=248/8700/91 nM, respectively).
BI 1015550 displays no significant activity agianst human PDE7A and human PDE3A, and PDE1C, PDE9A, human PDE2A and PDE5 at 10 uM.
BI 1015550 inhibited LPS-induced TNF- α release with an IC50 35 nM in human PBMCs, inhibited phytohemagglutinin P-induced IL-2 release with IC50 of 9 nM.
BI 1015550 completely inhibited LPS-stimulated TNF-α release with an IC50 in rat whole blood, inhibited TNF-α release up to 70–80% with an IC50 of 670 nM human whole blood.
BI 1015550 (0.01, 0.1, and 1 mg/kg, p.o.) inhibited LPS-stimulated TNF-α release in whole blood ex vivo in mice with ED50 of 0.04 mg/kg.
BI 1015550 (0.01, 0.1, and 1 mg/kg, p.o.) inhibited LPS-induced lung neutrophil influx in male Wistar rats with an ED50 of 0.1 mg/kg.
BI 1015550 inhibited α-SMA protein expression of TGF-β-stimulated IPF-LF with an IC50 of 210 nM, showed a synergistic effect in combination with Nintedanib on fibroblast proliferation.
BI 1015550 is a promising oral clinical candidate for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibro-proliferative diseases.