Tetrahydro-3H-pyrazolo[4,3-a]phenanthridine-based CDK inhibitor

Chem Commun (Camb). 2018 May 1;54(36):4521-4524. doi: 10.1039/c8cc01154k.

Abstract

Cyclin-dependent kinases have emerged as important targets for cancer therapy. HSD992, containing a novel scaffold based on the tetrahydro-3H-pyrazolo[4,3-a]phenanthridine core, inhibits CDK2/3 but not other CDKs and also potently inhibits several cancer cell lines.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Catalytic Domain
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 2 / chemistry
  • Cyclin-Dependent Kinase 3 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 9 / antagonists & inhibitors
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / chemistry
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Docking Simulation
  • Phenanthridines / chemical synthesis
  • Phenanthridines / chemistry
  • Phenanthridines / pharmacology*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Staurosporine / pharmacology

Substances

  • Antineoplastic Agents
  • Phenanthridines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • CDK2 protein, human
  • CDK3 protein, human
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 3
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases
  • Staurosporine