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

International Journal of Molecular Sciences

Xiaoyun Wu¹  Shanhe Wan² 

[1] School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; E-Mail

关键词: 3D-QSAR;    CoMFA;    CoMSIA;    JAK2 inhibitor;    5H-pyrido[4;    3-b]indol-4-carboxamide;   

DOI  :  10.3390/ijms140612037

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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