LPi-1 is a highly potent, selective and ATP-competitive inhibitor of large tumor suppressor kinases (LATS1 and LATS2) with IC50 of 4.4 nM and 1.3 nM respectively, abrogates the LATS1/2-mediated YAP1 inhibition in cells, activates YAP1 and its paralogue TAZ in vitro and in vivo.
LPi-1 inhibits LATS1- or LAST2-mediated phosphorylation of YAP1 in a dose-dependent and time-dependent manner.
LPi-1 displaysa high-affinity interaction with the LATS1 and LATS2 proteins, with Kd values of 243.3 and 111.6  nM, respectively, in MST assays.
LPi-1 reduces the phosphorylation of endogenous YAP1 in a dose-dependent manner across various cell lines, including HepG2, HEK293T, Bel7404, HeLa, SNU-423, HCT116, U2OS and primary mouse hepatocytes.
LPi-1 effectively blocked Hippo signalling activity in HepG2 cells.
LPi-1 (10 mg/kg, i.p.) promotes the activation of YAP in vivo in in ICR mouse without any apparent side effects.
LPi-1 (3 mg/kg) promotes liver repair and regeneration in mice, ameliorates paracetamol (APAP)-induced liver injury.
LPi-1 provides protection against dextran sulphate sodium salt (DSS)-induced colitis in mice.