Started by drunkenshoe, August 03, 2023, 07:02:38 AM
QuoteAbstractTargeting transcription replication conflicts, a major source of endogenous DNA double-stranded breaks and genomic instability could have important anticancer therapeutic implications. Proliferating cell nuclear antigen (PCNA) is critical to DNA replication and repair processes. Through a rational drug design approach, we identified a small molecule PCNA inhibitor, AOH1996, which selectively kills cancer cells. AOH1996 enhances the interaction between PCNA and the largest subunit of RNA polymerase II, RPB1, and dissociates PCNA from actively transcribed chromatin regions, while inducing DNA double-stranded breaks in a transcription-dependent manner. Attenuation of RPB1 interaction with PCNA, by a point mutation in RPB1's PCNA-binding region, confers resistance to AOH1996. Orally administrable and metabolically stable, AOH1996 suppresses tumor growth as a monotherapy or as a combination treatment but causes no discernable side effects. Inhibitors of transcription replication conflict resolution may provide a new and unique therapeutic avenue for exploiting this cancer-selective vulnerability.
Quote from: drunkenshoe on August 03, 2023, 07:02:38 AMAnyone's seen this? Well, this kind of news are on and off about a few times a year, but it looks good. The medicine is in phase one.https://pubmed.ncbi.nlm.nih.gov/37531956/Small molecule targeting of transcription-replication conflict for selective chemotherapy (July 2023)Protein Destroys 'Hard to Treat' Cancers, Could Become 'One Size Fits All' Pill (Jun 2023)https://www.goodnewsnetwork.org/university-of-texas-cancer-breakthrough-erx-41/