Discovery of TK-642 as a highly potent, selective, orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2 IC = 2.7 nmol/L) with favorable pharmacokinetic profiles ( = 42.

Corrosion Fatigue Fracture Characteristics of FSW 7075 Aluminum Alloy Joints.

The corrosion fatigue properties and fracture characteristics of friction stir welding joints of 7075 aluminum alloys were studied via corrosion fatigue tests, electrochemical measurements, and corrosion fatigue morphology and microstructure observations. The results show that the corrosion fatigue crack of the friction stir welding (FSW) joint of 7075 aluminum alloys originated in the junction zone between the thermomechanically affected zone and the weld nugget zone. The corrosion fatigue life of the joint decreased with increasing stress amplitude, with an S-N curve equation of lgN = 5.

Research on Residual Stress of a BS700 Butt-Welded Box Section and Its Influence on the Stability of Axial Compression Members.

BS700 high-strength steel is widely used in engineering. Welding residual stress during the manufacturing process has a significant influence on the structural safety and service life of steel structures. In this study, the residual stress of a BS700 butt-welded box section axial compression member was studied by the blind-hole method, its distribution law was summarized, and a residual stress distribution model was established.