PV-1019 / Provid - LARVOL DELTA

Combination of CHK1 and CHK2 inhibitors exerts synergistic antitumor effects against neuroblastoma cells. (PubMed, Pediatr Res) - "Combined CHK1/CHK2 inhibitor therapy shows a synergistic anti-tumor effect against neuroblastoma cells. Combination therapy impairs DNA damage response pathways and drives accelerated cell cycle progression in neuroblastoma cells. Combination therapy increases DNA damage, replication stress, and apoptosis marker expression. Combined CHK1/CHK2 inhibition holds therapeutic potential for the treatment of neuroblastoma."

Journal • Neuroblastoma • Oncology • Solid Tumor • CASP3 • MYCN • RPA2

Natural podophyllotoxin analog 4DPG attenuates EMT and colorectal cancer progression via activation of checkpoint kinase 2. (PubMed, Cell Death Discov) - "In this study, we observed that epithelial colorectal cancer (CRC) cells transiently exposed to 5-fluorouracil (5-FU) (a chemotherapeutic drug for CRC) as well as 5-FU-resistant cells (5-FU-R) develop EMT characters as evidenced by activation of Vimentin and augmented invasive properties...Mechanistically, SiRNA-mediated silencing of Chk2, as well as treatment with Chk2-specific small-molecule inhibitor (PV1019), divulges that 4DPG represses Vimentin activation in a Chk2-dependent manner...In addition, 4DPG confers suitable pharmacokinetic properties and strongly abrogates tumor growth, polyps formation, and lung metastasis in an orthotopic rat colorectal carcinoma model. In conclusion, our findings demonstrate 4DPG as a targeted antitumor/anti-metastatic pharmacological lead compound to circumvent EMT-associated drug resistance and suggest its clinical benefits for the treatment of aggressive cancers."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • CDH1 • CHEK2 • MMP2 • TIMP1 • VIM