In-Silico Drug discovery approach targeting receptor tyrosine kinase-like orphan receptor 1 for cancer treatment

Sci Rep. 2017 Apr 21;7(1):1029. doi: 10.1038/s41598-017-01254-w.

Abstract

Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils. The prediction of the active site revealed its cage-like function that opens for ligand entry and then closes for interacting with the ligands. Optimized ligands from the database were virtually screened to obtain the most efficient and potent ones. The screened ligands were evaluated for their therapeutic usefulness. Furthermore, the ligands that passed the test were docked to the target protein resulting in a few ligands with high score, which were analyzed further. The highest scoring ligand, Beta-1, 2,3,4,6-Penta-O-Galloyl-D-Glucopyranose was reported to be a naturally occurring tannin. This in silico approach indicates the potential of this molecule for advancing a further step in cancer treatment.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Catalytic Domain
  • Computer Simulation
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Structure, Secondary
  • Receptor Tyrosine Kinase-like Orphan Receptors / antagonists & inhibitors
  • Receptor Tyrosine Kinase-like Orphan Receptors / chemistry*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ROR1 protein, human
  • Receptor Tyrosine Kinase-like Orphan Receptors