Subject collection: Model Systems in Drug Discovery
- Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds
Summary: Myotonic dystrophy muscle cell models displaying characteristic disease-associated molecular features can be used to investigate molecular pathophysiological mechanisms and evaluate therapeutic approaches.
- Miconazole protects blood vessels from MMP9-dependent rupture and hemorrhage
Summary: A phenotype-based chemical screen in zebrafish identifies miconazole as a novel hemorrhagic suppressor. Miconazole inhibits vessel rupture and hemorrhages by decreasing pErk and MMP9 in zebrafish and rats.
- Seizure control through genetic and pharmacological manipulation of Pumilio in Drosophila: a key component of neuronal homeostasis
Summary: Next-generation anticonvulsant compounds potentiate the activity of the neuronal homeostatic regulator Pumilio.
- Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models
Summary: Lurbinectedin-gemcitabine synergism in PDA models involves lurbinectedin-induced tumor macrophage depletion, triggering CDA downregulation and enhanced DNA damage, supporting the use of this combination to treat macrophage-infiltrated pancreatic tumors.
- Drug screening using model systems: some basics
Summary: The author provides some tips on what to consider before you begin drug screening.
- Seeking out the sweet spot in cancer therapeutics: an interview with Lewis Cantley
Summary: We spoke to Lewis Cantley about his career path and the story behind some of his key breakthroughs, including discovery of the phosphoinositide 3-kinase signaling pathway and insights into the role of dysregulated metabolism in cancer.
- A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses
Editors' choice: Clinically observed drug response differentials to β-blocker and flecainide treatment in catecholaminergic polymorphic ventricular tachycardia can be modeled in vitro using patient-derived iPSC-cardiomyocytes.
- The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN
Summary: Our results suggest that PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients.
- A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition
Editors' choice: In vivo validation of a potent DYRK1A inhibitor, with proven clinical safety, using Down-syndrome- and Alzheimer's-disease-like models.
- Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers
Editors' choice: Personalized therapeutic targets for triple-negative breast cancers remain an important unmet clinical need. Genomic profiling of murine Trp53-null tumors identified a number of promising drug targets conserved in humans.