RESUMEN
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.
Asunto(s)
Antígenos de Superficie , Antineoplásicos , Glutamato Carboxipeptidasa II , Inhibidores de Proteasoma , Humanos , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/química , Inhibidores de Proteasoma/síntesis química , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Glutamato Carboxipeptidasa II/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antígenos de Superficie/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismoRESUMEN
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. Here, we report an unusual, short-duration proton event detected on 5 June 2011 in the compressed sheath region bounded by an interplanetary shock and the leading edge of the interplanetary CME (or ICME) that was driving the shock. While < 10 MeV protons were detected already at the shock front, the higher-energy (> 30 MeV) protons were detected about four hours after the shock arrival, apparently correlated with a turbulent magnetic cavity embedded in the ICME sheath region.