Challenges and opportunities in cancer drug resistance

RA Ward, S Fawell, N Floc'h, V Flemington… - Chemical …, 2020 - ACS Publications
There has been huge progress in the discovery of targeted cancer therapies in recent years.
However, even for the most successful and impactful cancer drugs which have been …

RAF-MEK-ERK pathway in cancer evolution and treatment

R Ullah, Q Yin, AH Snell, L Wan - Seminars in cancer biology, 2022 - Elsevier
Abstract The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway
involved in cell proliferation and survival. The three-layered MAPK signaling cascade is …

Emerging strategies to target RAS signaling in human cancer therapy

K Chen, Y Zhang, L Qian, P Wang - Journal of hematology & oncology, 2021 - Springer
Abstract RAS mutations (HRAS, NRAS, and KRAS) are among the most common
oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring …

An analysis of successful hit-to-clinical candidate pairs

DG Brown - Journal of medicinal chemistry, 2023 - ACS Publications
An analysis of 156 published clinical candidates from the Journal of Medicinal Chemistry
between 2018 and 2021 was conducted to identify lead generation strategies most …

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis

JDG Leach, N Vlahov, P Tsantoulis… - Nature …, 2021 - nature.com
Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct
mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch …

Targeting extracellular signal-regulated protein kinase 1/2 (ERK1/2) in cancer: an update on pharmacological small-molecule inhibitors

L Fu, S Chen, G He, Y Chen, B Liu - Journal of medicinal chemistry, 2022 - ACS Publications
Extracellular signal-regulated protein kinase 1/2 (ERK1/2), the only known substrate of
MEK1/2, is located downstream of the RAS-RAF-MEK-ERK (MAPK) pathway and is …

Navigating the ERK1/2 MAPK cascade

A Martin-Vega, MH Cobb - Biomolecules, 2023 - mdpi.com
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological
processes including proliferation, cell cycle control, growth, and survival; common across all …

[HTML][HTML] Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy

X Pan, J Pei, A Wang, W Shuai, L Feng, F Bu… - … Pharmaceutica Sinica B, 2022 - Elsevier
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2
(ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its …

Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2

JW Anderson, D Vaisar, DN Jones, LM Pegram… - Elife, 2024 - elifesciences.org
Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has
been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium …

Design, synthesis, and biological evaluation of pyrrole-2-carboxamide derivatives as mycobacterial membrane protein large 3 inhibitors for treating drug-resistant …

H Zhao, Y Gao, W Li, L Sheng, K Cui… - Journal of medicinal …, 2022 - ACS Publications
In this work, pyrrole-2-carboxamides were designed with a structure-guided strategy based
on the crystal structure of MmpL3 and a pharmacophore model. The structure–activity …