Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors

Zaraei, Seyed–Omar; Sbenati, Rawan M.; Alach, Nour N.; Anbar, Hanan S.; El-Gamal, Randa; Tarazi, Hamadeh; Shehata, Mahmoud K.; Abdel‐Maksoud, Mohammed S.; Oh, Chang‐Hyun; El–Gamal, Mohammed I.

doi:10.1016/j.ejmech.2021.113674

Cited by 14 publications

(8 citation statements)

References 32 publications

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“…Pyrimidinyl nitrogen, sulfonyl oxygen, imidazo[2,1- b ]thiazole nitrogen, and benzyloxy oxygen accept the five hydrogen bonds. In addition, the benzyl ring forms hydrophobic interaction with Phe862 [ 161 ].…”

Section: Her4 Inhibitorsmentioning

confidence: 99%

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A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

et al. 2021

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HER4 is a receptor tyrosine kinase that is required for the evolution of normal body systems such as cardiovascular, nervous, and endocrine systems, especially the mammary glands. It is activated through ligand binding and activates MAPKs and PI3K/AKT pathways. HER4 is commonly expressed in many human tissues, both adult and fetal. It is important to understand the role of HER4 in the treatment of many disorders. Many studies were also conducted on the role of HER4 in tumors and its tumor suppressor function. Mostly, overexpression of HER4 kinase results in cancer development. In the present article, we reviewed the structure, location, ligands, physiological functions of HER4, and its relationship to different cancer types. HER4 inhibitors reported mainly from 2016 to the present were reviewed as well.

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Section: Her4 Inhibitorsmentioning

confidence: 99%

“… Putative binding interactions of compound I with HER4 active site [ 161 ]. Reprinted with permission from ref.…”

Section: Figurementioning

confidence: 99%

A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

et al. 2021

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“…also beyond the EGFR family) [89]. Potentially, a recently synthesized kinase inhibitor with enhanced selectivity for HER4 is more suitable for specific receptor targeting [111], presumed that HER4 takes tumorpromoting effect. However, a kinase inhibitor would most probably not inhibit HER4 receptor cleavage and the phosphorylationindependent signaling of 4ICD.…”

Section: The Potential Of Therapeutic Anti-her4 Targetingmentioning

confidence: 99%

“Shedding” light on HER4 signaling in normal and malignant breast tissues

Brockhoff

2022

Cellular Signalling

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“…[1] Its incidence is reported to reach about 29.5 million cases each year in 2040. [2,3] Liver cancer ranks sixth in the world among all malignancies. It's considered the third most deadly cancer type among all.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Anticancer Evaluation and Molecular Modeling Studies of New Thiazolidinone‐Benzoate Scaffold as EGFR Inhibitors, Cell Cycle Interruption and Apoptosis Inducers in HepG2

Magdy Eldaly,

Salama Zakaria,

Hanafy Metwally

2023

Chemistry & Biodiversity

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Synthesis of new anticancer candidates with protein kinases inhibitory potency is a major goal of pharmaceutical science and synthetic research. This current work represents the synthesis of a series of substituted benzoate‐thiazolidinones. Most prepared thiazolidinones were evaluated in vitro for their potential anticancer activity against three cell lines by MTT assay, and they found to be more effective against cancer cell lines with no harm toward normal cells. Thiazolidinones 5 c and 5 h were further evaluated to be kinase inhibitors against EGFR showing effective inhibitory impact (with IC50 value; 0.2±0.009 and 0.098±0.004 μM, for 5 c and 5 h, respectively). Furthermore, 5 c and 5 h have effects on cell cycle and apoptosis induction capability in HepG2 cell lines by DNA‐flow cytometry analysis and annexin V‐FITC apoptosis assay, respectively. The results showed that they have effect of disrupting the cell cycle and causing cell mortality by apoptosis in the treated cells. Moreover, molecular docking studies showed better binding patterns for 5 c and 5 h with the active site of the epidermal growth factor receptor (EGFR) protein kinase (PDB code 1M17). Finally, toxicity risk and physicochemical characterization by Osiris method was performed on most of the compounds, revealing excellent properties as possible drugs.

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Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors

Cited by 14 publications

References 32 publications

A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

“Shedding” light on HER4 signaling in normal and malignant breast tissues

Design, Synthesis, Anticancer Evaluation and Molecular Modeling Studies of New Thiazolidinone‐Benzoate Scaffold as EGFR Inhibitors, Cell Cycle Interruption and Apoptosis Inducers in HepG2

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