ArticleInvestigational new drugs2019
Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types.
Article in Investigational new drugs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Mechanistic evaluation of NSC 57774 as a SHP2 inhibitor in gastric cancer: Multi-pathway signaling modulation in vitro.PloS one · 2026Article
- Decoding breast cancer: insights into molecular pathways & therapeutic approaches.Discover oncology · 2025Review
- SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model.Neuro-oncology · 2025Article
- Design, Synthesis, Antitumor Activity Evaluation, and Molecular Dynamics Simulation of Some 2-aminopyrazine Derivatives.Current computer-aided drug design · 2025Article
- Discovery of a novel SHP2 allosteric inhibitor using virtual screening, FMO calculation, and molecular dynamic simulation.Journal of molecular modeling · 2024Article
- Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives.iScience · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- SHP2 is involved in the occurrence, development and prognosis of cancer.Oncology letters · 2023Article
- Ajuforrestin A, an Abietane Diterpenoid fromMolecules (Basel, Switzerland) · 2022Article
- Dissecting protein tyrosine phosphatase signaling by engineered chemogenetic control of its activity.The Journal of cell biology · 2022Article
- Knockdown of RNF183 suppressed proliferation of lung adenocarcinoma cellsCell cycle (Georgetown, Tex.) · 2022Article
- Health benefits of cyanidin-3-glucoside as a potent modulator of Nrf2-mediated oxidative stress.Inflammopharmacology · 2021Review
- SHP2 Targets ITK Downstream of PD-1 to Inhibit T Cell Function.Inflammation · 2021Article
- A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Article
- SHP2 knockdown ameliorates liver insulin resistance by activating IRS-2 phosphorylation through the AKT and ERK1/2 signaling pathways.FEBS open bio · 2020Article
- Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to ArrestBioMed research international · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinases and phosphatases are important players in growth signaling and are involved in cancer development. For development of targeted cancer therapy, attention is given to kinases rather than phosphatases inhibitors. Src homology region 2 domain-containing protein tyrosine phosphatase2 (SHP2) is overexpressed in different types of cancers. We investigated the SHP2-inhibitory effects of two new 5-aminosalicylate-4-thiazolinones in human cervical (HeLa) and breast (MCF-7 & MDA-MB-231) cancer cells. In-silico molecular docking showed preferential affinity of the two compounds towards the catalytic over the allosteric site of SHP2. An enzymatic assay confirmed the docking results whereby 0.01 μM of both compounds reduced SHP2 activity to 50%. On cellular level, the two compounds significantly reduced the expression of SHP2, KRAS, p-ERK and p-STAT3 in HeLa but not in the other two cell lines. Phosphorylation of AKT and JNK was enhanced in HeLa and MCF7. Both compounds exhibited anti-proliferative/anti-migratory effects on HeLa and MCF7 but not in MDA-MB-231 cells. These results indicate that inhibition of SHP2 and its downstream pathways by the two compounds might be a promising strategy for cancer therapy in some but not all cancer types.
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