Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors

Takarada, Jéssica E.; Cunha, Micael R.; Almeida, Vitor M.; Vasconcelos, Stanley N.S.; Santiago, André S.; Godoi, Paulo H.; Salmazo, Anita; Ramos, Priscila Z.; Fala, Angela M.; de Souza, Lucas R.; Da Silva, Italo E.P.; Bengtson, Mario H.; Massirer, Katlin B.; Couñago, Rafael M.

doi:10.1016/j.bmc.2023.117561

Bioorganic & Medicinal Chemistry

2024

DOI: 10.1016/j.bmc.2023.117561

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Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors

Jéssica E. Takarada,

Micael R. Cunha,

Vitor M. Almeida

et al.

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2024

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Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer

Alsharoh,

Chiroi,

Isachesku

et al. 2024

Biomedicines

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Lung cancer (LC) is a highly invasive malignancy and the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) as its most prevalent histological subtype. Despite all breakthroughs achieved in drug development, the prognosis of NSCLC remains poor. The mitogen-activated protein kinase signaling cascade (MAPKC) is a complex network of interacting molecules that can drive oncogenesis, cancer progression, and drug resistance when dysregulated. Over the past decades, MAPKC components have been used to design MAPKC inhibitors (MAPKCIs), which have shown varying efficacy in treating NSCLC. Thus, recent studies support the potential clinical use of MAPKCIs, especially in combination with other therapeutic approaches. This article provides an overview of the MAPKC and its inhibitors in the clinical management of NSCLC. It addresses the gaps in the current literature on different combinations of selective inhibitors while suggesting two particular therapy approaches to be researched in NSCLC: parallel and aggregate targeting of the MAPKC. This work also provides suggestions that could serve as a potential guideline to aid future research in MAPKCIs to optimize clinical outcomes in NSCLC.

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Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer

Alsharoh,

Chiroi,

Isachesku

et al. 2024

Biomedicines

View full text Add to dashboard Cite

show abstract

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Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors

Cited by 1 publication

References 65 publications

Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer

Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer

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