The purpose of this study is to evaluate the safety and tolerability of XL418 in subjects with solid tumors. XL418 is a new chemical entity that inhibits a spectrum of targets, including Akt and p70S6K, that mediate PI3 Kinase / PTEN signaling.

开始日期2007-04-01

申办/合作机构

Exelixis, Inc.

100 项与 XL-418 相关的临床结果

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100 项与 XL-418 相关的转化医学

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100 项与 XL-418 相关的专利（医药）

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项与 XL-418 相关的文献（医药）

International Journal of Molecular Sciences2区 · 生物学

Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19

2区 · 生物学

ArticleOA

作者: Peslherbe, Gilles H. ; Kaliamurthi, Satyavani ; Singh, Sanjeev Kumar ; Selvaraj, Gurudeeban ; Wei, Dong-Qing ; Selvaraj, Chandrabose

Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton’s tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.

100 项与 XL-418 相关的药物交易

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