3D-QSAR analysis of benzimidazole inhibitors of interleukin-2 inducible T cell kinase (ITK) considering receptor flexibility and water importance for molecular alignment

Malkeet Singh Bahia; Om Silakari

doi:10.1007/s00044-013-0548-x

3D-QSAR analysis of benzimidazole inhibitors of interleukin-2 inducible T cell kinase (ITK) considering receptor flexibility and water importance for molecular alignment

Malkeet Singh Bahia, Om Silakari

Punjabi University

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Interleukin-2 inducible T cell kinase (ITK) plays an essential role in T cell development, differentiation, and production of Th 2 pro-inflammatory cytokines, such as IL-2, IL-4, IL-5, IL-10, IL-13, and IL-17. Since this kinase is an important contributor in Th 2 cell-mediated autoimmune and allergic disease conditions, e.g. psoriasis, atopic dermatitis, and allergic asthma, the potent inhibitors of ITK may serve as potential therapeutic agents for the treatment of these disease conditions. Thus, a set of 176 benzimidazole ITK inhibitors was employed to perform 3D-QSAR analysis considering the importance of water molecules for docking-based molecular alignment. The best 3D-QSAR model was selected on the basis of the highest value of Q ² _test (0.609). The selected model also displayed the highest values of R ² _train (0.973), F (536.2), and the lowest SD (0.163). The contour plots for different properties would provide beneficial guidance for designing new potent congeners.

Original language	English
Pages (from-to)	5578-5587
Number of pages	10
Journal	Medicinal Chemistry Research
Volume	22
Issue number	11
DOIs	https://doi.org/10.1007/s00044-013-0548-x
State	Published - Nov 2013
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments The authors thank Dr. Ravikumar Muttineni (Application Scientist), Er. Anirban Banerjee (IT Consultant), and Mr. Raghu Rangaswamy from Schrödinger, Bangalore, for their constant scientific and technical support to handle Schrödinger software and work smoothly. The authors also thank University Grant Commission, New Delhi for providing the financial support; Grant No. 37-324/2009(SR).

Funding

Acknowledgments The authors thank Dr. Ravikumar Muttineni (Application Scientist), Er. Anirban Banerjee (IT Consultant), and Mr. Raghu Rangaswamy from Schrödinger, Bangalore, for their constant scientific and technical support to handle Schrödinger software and work smoothly. The authors also thank University Grant Commission, New Delhi for providing the financial support; Grant No. 37-324/2009(SR).

Funders	Funder number
University Grants Commission	37-324/2009

Keywords

Atom-based 3D-QSAR
Interleukin-2 inducible T cell kinase (ITK)
PHASE
Receptor flexibility
Rheumatoid arthritis

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abstract = "Interleukin-2 inducible T cell kinase (ITK) plays an essential role in T cell development, differentiation, and production of Th 2 pro-inflammatory cytokines, such as IL-2, IL-4, IL-5, IL-10, IL-13, and IL-17. Since this kinase is an important contributor in Th 2 cell-mediated autoimmune and allergic disease conditions, e.g. psoriasis, atopic dermatitis, and allergic asthma, the potent inhibitors of ITK may serve as potential therapeutic agents for the treatment of these disease conditions. Thus, a set of 176 benzimidazole ITK inhibitors was employed to perform 3D-QSAR analysis considering the importance of water molecules for docking-based molecular alignment. The best 3D-QSAR model was selected on the basis of the highest value of Q 2 test (0.609). The selected model also displayed the highest values of R 2 train (0.973), F (536.2), and the lowest SD (0.163). The contour plots for different properties would provide beneficial guidance for designing new potent congeners.",

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3D-QSAR analysis of benzimidazole inhibitors of interleukin-2 inducible T cell kinase (ITK) considering receptor flexibility and water importance for molecular alignment

Abstract

Bibliographical note

Funding

Keywords

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