Synthesis and biological evaluation of BU-4664L derivatives as potential anticancer agents.

BU-4664L is a naturally occurring N-farnesylated dibenzodiazepinone with important biological activities. Herein, we report the synthesis and antitumor evaluation of two series of BU-4664L derivatives bearing different substituent patterns on the dibenzodiazepinone core and with diverse side chains. All of the derivatives displayed micromolar activity against the human prostate cancer PC-3 cells, while lower or no activity against the human lung H460 cells.

Recent Advances in the Development of Casein Kinase 1 Inhibitors.

Background: The casein kinase 1 (CK1) family is involved in regulating many cellular processes, including membrane trafficking, DNA damage repair, cytoskeleton dynamics, cytoskeleton maintenance and apoptosis. CK1 isoforms, especially CK1δ and CK1ε have emerged as important therapeutic targets for severe disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer. Due to the importance of CK1 for the pathogenesis of disorders, there are great interests in the development of CK1 inhibitors.

Tubulin Maytansine Site Binding Ligands and their Applications as MTAs and ADCs for Cancer Therapy.

Background: Microtubule Targeting Agents (MTAs) represent the most successful anticancer drugs for cancer chemotherapy. Through interfering with the tubulin polymerization and depolymerization dynamics, MTAs influence intracellular transport and cell signal pathways, inhibit cell mitosis and cell proliferation, and induce cell apoptosis and death. The tubulin maytansine site binding agents are natural or nature-derived products that represent one type of the MTAs that inhibit tubulin polymerization and exhibit potent antitumor activity both in vitro and in vivo.