Shp2 is a ubiquitously expressed protein tyrosine phosphatase (PTP) related to adult acute myelogenous leukemia and human solid tumors. In this report, we describe identification of a potent Shp2 inhibitor, Fumosorinone (Fumos) from entomogenous fungi, which shows selective inhibition of Shp2 over other tested PTPs. Using a surface plasmon resonance analysis, we further confirmed the physical interaction between Shp2 and Fumos. Fumos inhibits Shp2-dependent activation of the Ras/ERK signal pathway downstream of EGFR and interrupts EGF-induced Gab1-Shp2 association. As expected, Fumos shows little effects on the Shp2-independent ERK1/2 activation induced by PMA or oncogenic Ras. Furthermore, Fumos down-regulates Src activation, inhibits phosphorylation of Paxillin and prevents tumor cell invasion. These results suggest that Fumos can inhibit Shp2-dependent cell signaling in human cells and has a potential for treatment of Shp2-associated diseases.

Two new oxysporone derivatives, pestalrone A (1) and pestalrone B (2), along with two known structurally related compounds 3,4, were from the fermentation broth of the endophytic plant fungus Pestalotiopsis karstenii isolated from stems of Camellia sasanqua. Their structures and relative configurations were elucidated by extensive spectroscopic analysis and comparison of chemical shifts with related known compounds. Compound 2 exhibited significant activities agains HeLa, HepG2 and U-251 with IC₅₀ values of 12.6, 31.7 and 5.4 µg/mL, respectively.

Three new pigment compounds—terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3)—were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1) inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC₅₀ values 12.5, >50, 4.1, 10.6, 5.6 µg/mL, respectively; pinophilin C (2) with IC₅₀ values 6.8, 8.0, 4.5, 4.7, 3.4 µg/mL, respectively; and cryptosporioptide A (3) with IC₅₀ values 7.3, 5.7, 7.6, >50, 4.9 µg/mL, respectively.