canertinib (CI-1033)

In our previous study, we found that chemical inhibition of EGFR utilizing Canertinib, dramatically reduced hepatocyte steatosis, liver injury, and fibrosis, in a murine fast-food diet (FFD) model, indicating a potential role for EGFR in regulating NAFLD... The hepatocyte-specific deletion of EGFR alters lipid metabolism and fibrosis signaling in a murine FFD model of NAFLD, but is much less effective compared to pharmacological inhibition of EGFR.

ErbB inhibitors (canertinib and sapitinib) or erbB3 knockdown in combination with Src (saracatinib), calmodulin [trifluoperazine (TFP)], or proviral integration site of Moloney murine leukemia kinase (AZD1208) inhibition even more effectively reduces proliferation and survival. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events and when combined with trifluoperazine even more effectively reduces proliferation and survival compared to monotherapy. Our findings implicate erbB3, calmodulin, PIM kinases and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective.

Additionally, afatinib and canertinib were recognized which might have potential therapeutic implications in MSC1, and the targets of these drugs presented a higher expression in both gene and protein levels in HCC. Our studies may provide a promising platform for improving prognosis and tailoring therapy in HCC.

Library screening revealed that erlotinib, canertinib, and lapatinib demonstrated inhibitory effects on cell migration. In addition, canertinib treatment restored E-cadherin expression and reduced the expression of epithelial-mesenchymal transition regulatory factors such as Slug and Snail. Taken together, these results suggest that EGFR/HER2 inhibitors are potential therapeutic options for BCAR4 fusion-harboring lung cancer patients, even in the absence of EGFR mutations.

Using available genetic atlas data, potential drug candidates for treatment of pNETs were identified based on differentially expressed genes. These results may help focus efforts on identifying targeted agents with therapeutic efficacy to treat patients with pNETs.

The ErbB2 phosphorylation inhibitor (CI-1033) and GDF15 knockout cell lines were used to appraise the role of ErbB2 and GDF15 in mediating the effects of M1-CM...Our results demonstrate that M1 macrophages induce the proliferation, migration, invasion, and xenograft development of OSCC cells. Mechanistically, this protumor effect of M1 macrophages is partly associated with inducing GDF15-mediated ErbB2 phosphorylation.

When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI-1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). GDF15 overexpression promotes OSCC proliferation via erbB2 phosphorylation. Thus, ErbB2 inhibitors may represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression.

Pre-incubation with canertinib, pomalidomide or ubiquitination inhibitor MLN4924 totally blocked EGFR degradation by PROTACs. Elevating autophagy activities enhanced EGFR degradation and cell apoptosis induced by PROTACs. Our research not only offered a novel PROTAC tool to target EGFR TKI drug resistance in lung cancer, but also firstly demonstrated that the involvement of autophagy/lysosome system in PROTAC- mediated target protein degradation.