Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven million compounds using virtual screening and in vitro analysis

J Enzyme Inhib Med Chem. 2016;31(3):425-33. doi: 10.3109/14756366.2015.1036049. Epub 2015 May 7.


Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of ∼7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85-1.58 μM. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out.

Keywords: ADME; CA IX inhibitors; carbonic anhydrase; molecular docking; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / isolation & purification
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Structure-Activity Relationship


  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases