De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvβ6 and αvβ8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed.

design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches.

The Effect of Obesity on Distal Radius Fractures: An Analysis from the NSQIP Database.

Unlabelled: The rate and severity of obesity has risen over the past 40 years, and class III (formerly morbid) obesity presents additional sequelae. The effect of obesity on the incidence and recovery of hand and wrist fractures remains unclear. We sought to quantify the relationship between class III obesity and postoperative distal radius fracture (DRF) complications.