April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
3D-QSAR and Docking Studies of the Activin Receptor-Like Kinase 5 Antagonists for Use in Glaucoma Filtration Surgery
Author Affiliations & Notes
  • W. J. Geldenhuys
    Pharmaceutical Sciences, Northeastern Ohio Univ College Of Pharmacy, Rootstown, Ohio
  • J. Sapitro
    Ophthalmology, Summa Health Systems, Akron, Ohio
  • M. Celmer
    Ophthalmology, Summa Health Systems, Akron, Ohio
  • H. Nakamura
    Ophthalmology, Summa Health System, Akron, Ohio
  • Footnotes
    Commercial Relationships  W.J. Geldenhuys, None; J. Sapitro, None; M. Celmer, None; H. Nakamura, None.
  • Footnotes
    Support  Summa foundation grant to HN and Ohio Regents/NEOUCOM seed grant to WG
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 701. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      W. J. Geldenhuys, J. Sapitro, M. Celmer, H. Nakamura; 3D-QSAR and Docking Studies of the Activin Receptor-Like Kinase 5 Antagonists for Use in Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2010;51(13):701.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : TGF-β activity has been implicated in ocular scarring in the eyes, including that following glaucoma filtration surgery.The development of kinase inhibitors for activin receptor-like kinase (ALK) 5 (also known as TGF-β receptor type I) is therapeutically important. The purpose of our study was to determine 3D-quantitiative structure-activity relationship (QSAR) between ALK-5 and its inhibitors.

Methods: : For the 3D-QSAR, we used a comparative molecular field analysis (CoMFA) model. The ALK-5 inhibitor SB-505124 was used as template molecule for the alignment of the compounds.

Results: : To train the CoMFA model, 17 previously published compounds where used and the resulted partial least squares cross-validated statistical model yielded a model with q2> 0.3. This model was tested with a small test set of 4 compounds to see how well it would be able to predict inhibition (pIC50) of the ALK-5 inhibitors. The CoMFA model correctly predicted the experimental inhibition of the kinase inhibitors correctly more than 90% of the time. Furthermore, docking studies successfully showed where the important hydrogen-bonds which are important for ALK-5 binding by these kinase inhibitors.

Conclusions: : These results from the CoMFA models could enable the development of novel inhibitors which can be used in the treatment of glaucoma filtration surgery

Keywords: wound healing • computational modeling • cytokines/chemokines 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.