Novel Targeted Therapeutics for Castration-Resistant Prostate Cancer
Abstract
The clinical potential of PARP-1 inhibitors has been increasingly recognized over the last years. The therapeutic utility of known PARP-1 inhibitors has been limited by their nonspecific activity. All conventional PARP-1 inhibitors have been designed as NAD-mimetics. Therefore, such compounds also inhibit other enzymes that use NAD, producing various off target effects. To address these limitations, we have developed a novel class of PARP-1inhibitors by targeting the histone-dependent route of PARP-1 activation, a mechanism that is unique to PARP-1. During the reported period we synthesized and tested a panel of novel PARP1 inhibitors. Several compounds demonstrated prominent antitumor activities. However, their ADME and pharmacokinetic properties were suboptimal. We are currently undertaking medicinal chemistry optimization approach to create novel chemical probes with improved functional characteristics. We anticipate that our experiments will identify potential recurrence/progression biomarkers of PC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2021
- Accession Number
- AD1191133
Entities
People
- Alexei Tulin
Organizations
- University of North Dakota