&lt;p&gt;Safety, tolerability, and pharmacokinetics of simotinib, a novel specific EGFR tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer: results of a phase Ib trial&lt;/p&gt;

Hu, Xingsheng; Han, Xiaohong; Yang, Sheng; Li, Ning; Wang, Lin; Mao, Hua; Shi, Yuankai

doi:10.2147/cmar.s189626

Cited by 5 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The alkylation of compound 45 by 3-bromopropanol 91 gave 92, which could afford simotinib on the reaction with 5,8-dioxa-10-azadispiro[0,2,3,4]undecane, as shown in Scheme 13. Target Kinases Mechanistic studies of simotinib showed the selective and dose-dependent inhibition of the EGFR with an IC50 value of 19.9 nM [147].…”

Section: Synthesismentioning

confidence: 99%

“…Mechanistic studies of simotinib showed the selective and dose-dependent inhibition of the EGFR with an IC 50 value of 19.9 nM [147].…”

Section: Target Kinasesmentioning

confidence: 99%

“…The results of the pharmacokinetic study of simotinib in healthy volunteers showed an average clearance (CL) T 1/2 of 8-12 hrs [147]. Phase Ib of simotinib was also performed in 41 patients with EGFR gene mutations [147].…”

Section: Biological Activitymentioning

confidence: 99%

“…The safety and pharmacokinetics of simotinib was evaluated in a Phase I clinical study in patients with NSCLC (ClinicalTrials.gov identifier: NCT01772732) [147]. The results revealed that at a dose of up to 650 mg, simotinib was well tolerated.…”

Section: Metabolismmentioning

confidence: 99%

See 3 more Smart Citations

Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism

et al. 2021

View full text Add to dashboard Cite

Targeting the EGFR with small-molecule inhibitors is a confirmed valid strategy in cancer therapy. Since the FDA approval of the first EGFR-TKI, erlotinib, great efforts have been devoted to the discovery of new potent inhibitors. Until now, fourteen EGFR small-molecule inhibitors have been globally approved for the treatment of different types of cancers. Although these drugs showed high efficacy in cancer therapy, EGFR mutations have emerged as a big challenge for these drugs. In this review, we focus on the EGFR small-molecule inhibitors that have been approved for clinical uses in cancer therapy. These drugs are classified based on their chemical structures, target kinases, and pharmacological uses. The synthetic routes of these drugs are also discussed. The crystal structures of these drugs with their target kinases are also summarized and their bonding modes and interactions are visualized. Based on their binding interactions with the EGFR, these drugs are also classified into reversible and irreversible inhibitors. The cytotoxicity of these drugs against different types of cancer cell lines is also summarized. In addition, the proposed metabolic pathways and metabolites of the fourteen drugs are discussed, with a primary focus on the active and reactive metabolites. Taken together, this review highlights the syntheses, target kinases, crystal structures, binding interactions, cytotoxicity, and metabolism of the fourteen globally approved EGFR inhibitors. These data should greatly help in the design of new EGFR inhibitors.

show abstract

Section: Synthesismentioning

confidence: 99%

“…Mechanistic studies of simotinib showed the selective and dose-dependent inhibition of the EGFR with an IC 50 value of 19.9 nM [147].…”

Section: Target Kinasesmentioning

confidence: 99%