Development of small molecule-drug conjugates based on derivatives of natural proteasome inhibitors that exhibit selectivity for PSMA-expressing cancer cells.

In this study, we have developedsmall molecule drug conjugates (SMDCs)consisting ofa prostate specific membrane antigen (PSMA) ligandand syringolin derivatives, which are potent proteasome inhibitors, to selectively deliver syringolin derivatives to prostate cancer cells. Two parent compounds were used for syringolin derivatives with different linkage sites. These SMDCs exhibited PSMA-expressing cell-selective cytotoxicity and they could potentially be used for safer treatment of cancer.

Unusual enhancement of ~ 30 MeV proton flux in an ICME sheath region.

In gradual Solar Energetic Particle (SEP) events, shock waves driven by coronal mass ejections (CMEs) play a major role in accelerating particles, and the energetic particle flux enhances substantially when the shock front passes by the observer. Such enhancements are historically referred to as Energetic Storm Particle (ESP) events, but it remains unclear why ESP time profiles vary significantly from event to event. In some cases, energetic protons are not even clearly associated with shocks.