A5101842632- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- Synthesis and biological activity
- Cancer-related gene regulation
- 14-3-3 protein interactions
- Carbohydrate Chemistry and Synthesis
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
Italian Institute of Technology
2020-2025
University of Bologna
2024
Dublin City University
2024
GNA University
2024
National Research Council
2024
Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on possibility triggering synthetic using only small organic molecules (dubbed "fully small-molecule-induced lethality"). We exploited this to target pancreatic cancer, one major unmet needs oncology. discovered dihydroquinolone pyrazoline-based molecule (35d) that...
In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells G2/M, induces cell death, synergizes vinblastine. The compound destabilizes microtubules by acting as molecular plug that sterically inhibits curved-to-straight conformational switch α-tubulin subunit,...
Abstract The RAD51-BRCA2 interaction is central to DNA repair through homologous recombination. Emerging evidence indicates RAD51 overexpression and its correlation with chemoresistance in various cancers, suggesting inhibition as a compelling avenue for intervention. We previously showed that combining olaparib (a PARP inhibitor (PARPi)) RS -35d BRCA2-RAD51 inhibitor) was efficient killing pancreatic ductal adenocarcinoma (PDAC) cells. However, impaired cell viability even when administered...
Abstract In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells G2/M, induces cell death, synergizes vinblastine. The compound destabilizes microtubules by acting as molecular plug that sterically inhibits curved‐to‐straight conformational switch α‐tubulin...
Abstract The innovative framework of a fully small molecule-induced synthetic lethality gained increasing attention for its promising application in the selective eradication cancer cells. Disrupting interaction between BRCA2 and RAD51, key players DNA repair by homologous recombination (HR), represents an interesting option within paradigm. We previously showed that combining PARP inhibitor (PARPi) olaparib with BRCA2-RAD51 disruptor RS-35d , racemic dihydroquinolone pyrazoline-derivative...
e13577 Background: Aberrant CpG methylation of 14-3-3 σ promoters results in inactivation tumor suppressor genes induced response to DNA damage, and has been implicated G2/M cell cycle arrest by p53. The p53-regulated gene 14-3-3sigma undergoes frequent epigenetic silencing several types cancer including the breast. To correlation levels promoter 14-3-3σ with association prognostic factors breast cancer. Methods: This is a prospective study we quantified 107 women 108 control subjects Real...
Abstract DNA repair protein RAD51 is a key player in the homologous recombination pathway. Upon damage, transported into nucleus by BRCA2, where it can double‐strand breaks. Due to structural complexity and dynamics, researchers have not yet clarified mechanistic details of every step recruitment repair. possesses an intrinsic tendency form oligomeric structures, which make challenging conduct biochemical biophysical investigations. Here, for first time, we report on isolation...