Sperti Michela, Malavolta Marta, Ciniero Gloria, Borrelli Simone, Cavaglià Marco, Muscat Stefano, Tuszynski Jack Adam, Afeltra Antonella, Margiotta Domenico Paolo Emanuele, Navarini Luca
PolitoBIOMedLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
Dalle Molle Institute for Artificial Intelligence (IDSIA), Manno, Switzerland.
J Mol Graph Model. 2021 May;104:107789. doi: 10.1016/j.jmgm.2020.107789. Epub 2020 Nov 6.
The Janus Kinase signalling pathway is implicated in the pathogenesis of immune-related diseases. The potency of small-molecule Janus Kinase inhibitors in the treatment of inflammatory diseases demonstrates that this pathway can be successfully targeted for therapeutic purposes. The outstanding relevant questions concerning drugs' efficacy and toxicity challenge the research to enhance the selectivity of these drugs. The promising results of computational techniques, such as Molecular Dynamics and Molecular Docking, coupled with experimental studies, can improve the understanding of the molecular mechanism of Janus Kinase pathway and thus enable the rational design of new more selective inhibitor molecules.
Janus激酶信号通路与免疫相关疾病的发病机制有关。小分子Janus激酶抑制剂在治疗炎症性疾病方面的效力表明,该通路可成功作为治疗靶点。有关药物疗效和毒性的突出相关问题对提高这些药物选择性的研究提出了挑战。分子动力学和分子对接等计算技术与实验研究相结合所取得的有前景的结果,能够增进对Janus激酶通路分子机制的理解,从而实现新型更具选择性抑制剂分子的合理设计。