Corrigendum to “Discovery of novel taspine derivatives as antiangiogenic agents” [Bioorg. Med. Chem. Lett. 20 (2010) 718]

Zhang, Jie; Zhang, Yanmin; Zhang, San‐Qi; Wang, Sicen; He, Langchong

doi:10.1016/j.bmcl.2010.01.026

Cited by 21 publications

(25 citation statements)

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“…Docking experiments were carried out using the LeDock [29,30] program, which exhibits outstanding performance in protein-ligand flexible docking. The coordinate of EGFR was obtained from EGFR and lapatinib cocrystal structure (PDB:1XKK).…”

Section: Methodsmentioning

confidence: 99%

Intriguing generative metabolism discovery of reactive metabolite nitroso of lapatinib and relevant structural modification

Huang

Bai

Yang

2020

Int J of Quantum Chemistry

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Lapatinib is required as a therapy for advanced or metastatic breast cancer. However, its reactive metabolite (RM) nitroso was implicated in idiosyncratic hepatotoxicity.Density functional theory was performed to explore the metabolism of nitroso formation. Primary hydroxylation amine is a critical intermediate to produce nitroso.Three pathways from secondary alkylamine lapatinib to primary hydroxylation amine were designed and discussed. Calculation results show that it is difficult to form primary hydroxylation amine through common proposed hydrolysis nitrone with a barrier of 36.67 kcal/mol (path A), but it is smoothly formed by paths B and C with moderate determined barriers of 15.09 kcal/mol and 16.56 kcal/mol, respectively.Subsequently, we demonstrate that the mechanism of nitroso formation from primary hydroxylation amine should be a double hydrogen atom transfer rather than the previously proposed hydrolysis primary dihydroxylation amine. The barrier of the former is obviously lower than the latter. Based on metabolism results and structure analysis, several lapatinib derivatives are designed. Molecular docking of designed compounds with epidermal growth factor receptor (EGFR) shows that they share a similar binding mode with lapatinib. In particular, 2a to 2d show similar binding energy to lapatinib. This work showed metabolism details of nitroso formation from lapatinib and its structure modification, which can enrich the metabolism of amine drugs and provide guidance for drug optimization and design. K E Y W O R D Samine drug, lapatinib, nitroso, reactive metabolite, structure-based drug design

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Section: Methodsmentioning

confidence: 99%

Intriguing generative metabolism discovery of reactive metabolite nitroso of lapatinib and relevant structural modification

Huang

Bai

Yang

2020

Int J of Quantum Chemistry

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“…Highly efficient parallel syntheses were devised to prepare analogues for SAR studies, and a number of these 4-amino-6-benzimidazole-pyrimidines exhibited singledigit nanomolar IC 50 s against Lck in biochemical and cellular assays. 14 Using an iterative analogue library approach the SAR of an mGluR4 positive allosteric modulator lead based on a pyrazolo- [3,4-d]pyrimidine scaffold has been investigated. One compound, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described.…”

Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online

Terrett

2008

Combinatorial Chemistry - an Online Journal

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“…In a previous study, we demonstrated that taspine can inhibit tumor angiogenesis [11] and one of its mechanisms of action may involve inhibition of VEGFR-2 and the proliferation and migration of vascular endothelial cells [15,16]. Accordingly, considerable efforts to design, synthesize and evaluate taspine derivatives for cancer research have been made in recent years [17,18].…”

Section: Introductionmentioning

confidence: 97%

Revealing multi-binding sites for taspine to VEGFR-2 by cell membrane chromatography zonal elution

Wang

Ren

et al. 2012

Journal of Chromatography B

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Corrigendum to “Discovery of novel taspine derivatives as antiangiogenic agents” [Bioorg. Med. Chem. Lett. 20 (2010) 718]

Cited by 21 publications

References 0 publications

Intriguing generative metabolism discovery of reactive metabolite nitroso of lapatinib and relevant structural modification

Intriguing generative metabolism discovery of reactive metabolite nitroso of lapatinib and relevant structural modification

Combinatorial Chemistry Online

Revealing multi-binding sites for taspine to VEGFR-2 by cell membrane chromatography zonal elution

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