Fig. 1: Multi-functional kinase inhibitor LP-182 exhibits selectivity and specificity.
From: A lymphatic-absorbed multi-targeted kinase inhibitor for myelofibrosis therapy
a Targeting of downstream PI3K/mTOR and RAF/MEK signaling nodes by LP-182 in hematopoietic cells with constitutive JAK activation. b Single-point broad panel kinome screening against 2.5 μM LP-182. Average percent kinase inhibition from replicate data was input into Coral Human Kinome Visualization software, and analyzed as described in Methods61,62,63. Scaling for branch color, node color, and node size represents percent inhibition as indicated. Source data are provided as a Source Data file. Kinase families: Tyrosine kinase, TK; Tyrosine kinase-like, TKL; Serine/threonine kinase, STE; Casein kinase 1, CK1; Protein kinase A/G/C, AGC; Ca2+/calmodulin-dependent protein kinase, CAMK; CDK/MAPK/GSK/CDK-like, CMGC; Phosphoinositol kinases, PI Kinases. c Docked structures of LP-182 at the PI3Kγ (PDB code 3L08), mTOR1 (PDB code 4JSX), and BRAF (PDB code 5HI2) catalytic sites, and MEK1 (PDB code 3ORN) allosteric pocket as indicated28, 31,32,33. Molecular notation shows PI3K/mTOR inhibitor of LP-182 in blue, RAF/MEK inhibitor in orange, and polyethylene glycol linker in black. d Normalized fluorescence intensity values of phosphorylated AKT (pAKT; pS473) and ERK1/2 (pERK1/2; pT202/pY204) flow cytometry staining in SET-2 cells following treatment with indicated concentrations of LP-182 for 16 h. e Growth inhibition and Caspase activation values from SET-2 cells treated with indicated concentrations of LP-182 for 72 h or 48 h, respectively. Data represent the mean ± s.e.m., n = 3 independent experiments performed in replicate. Corrected data were normalized to vehicle treated control values and analyzed by non-linear regression where indicated. Source data are provided as a Source Data file.
