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Int. J. Mol. Sci. 2013, 14(6), 12037-12053; doi:10.3390/ijms140612037
Article

Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors

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Received: 7 April 2013; in revised form: 30 May 2013 / Accepted: 30 May 2013 / Published: 5 June 2013
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Abstract: Janus kinase 2 (JAK2) is an intracellular nonreceptor tyrosine kinase that belongs to the JAK family of kinases, which play an important role in survival, proliferation, and differentiation of a variety of cells. JAK2 inhibitors are potential drugs for the treatment of myeloproliferative neoplasms. The three dimensional quantitative structure-activity relationships have been studied on a series of JAK2 inhibitors by comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The CoMFA model had a cross-validated coefficient q2 of 0.633, and the relation non-cross-validated coefficient r2 of 0.976. The F value is 225.030. The contributions of steric and electrostatic fields to the activity are 55.2% and 44.8%, respectively. For the CoMSIA study, the q2, r2, and F values of the model are 0.614, 0.929, and 88.771, respectively. The contributions of steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond donor fields to the activity are 27.3%, 23.9%, 16.4%, 21.7%, and 10.7%, respectively. The CoMFA and CoMSIA models showed strong predictive ability, and the 3D contour plots give the basis on the structure modification of JAK2 inhibitors.
Keywords: 3D-QSAR; CoMFA; CoMSIA; JAK2 inhibitor; 5H-pyrido[4,3-b]indol-4-carboxamide 3D-QSAR; CoMFA; CoMSIA; JAK2 inhibitor; 5H-pyrido[4,3-b]indol-4-carboxamide
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wu, X.; Wan, S.; Zhang, J. Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors. Int. J. Mol. Sci. 2013, 14, 12037-12053.

AMA Style

Wu X, Wan S, Zhang J. Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors. International Journal of Molecular Sciences. 2013; 14(6):12037-12053.

Chicago/Turabian Style

Wu, Xiaoyun; Wan, Shanhe; Zhang, Jiajie. 2013. "Three Dimensional Quantitative Structure-Activity Relationship of 5H-Pyrido[4,3-b]indol-4-carboxamide JAK2 Inhibitors." Int. J. Mol. Sci. 14, no. 6: 12037-12053.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert