Bénédicte Dayde

Epoxy resins are widely used in the composite industry due to their dimensional stability, chemical resistance, and thermo-mechanical properties. However, these thermoset resins have important drawbacks. (i) The vast majority of epoxy matrices are based on non-renewable fossil-derived materials, and (ii) the highly cross-linked molecular architecture hinders their reprocessing, repairing, and recycling. In this paper, those two aspects are addressed by combining novel biobased epoxy monomers derived from renewable resources and dynamic crosslinks. Vanillin (lignin) and phloroglucinol (sugar bioconversion) precursors have been used to develop bi- and tri-functional epoxy monomers, diglycidyl ether of vanillyl alcohol (DGEVA) and phloroglucinol triepoxy (PHTE) respectively. Additionally, reversible covalent bonds have been incorporated in the network by using an aromatic disulfide-based diamine hardener. Four epoxy matrices with different ratios of epoxy monomers (DGEVA/PHTE wt%: 100/0, 60/40, 40/60, and 0/100) were developed and fully characterized in terms of thermal and mechanical properties. We demonstrate that their performances are comparable to those of commonly used fossil fuel-based epoxy thermosets with additional advanced reprocessing functionalities.

Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tumorigenesis processes. Antiproliferative activity studies using different cellular models led to the discovery of a lead candidate (6z) that combined both antiangiogenic and antitumoral effects. The activity of 6z was assessed against a panel of kinases and cell lines including solid cancers and leukemia cell models to explore its potential therapeutic applications. With its potency and selectivity for oncogenic kinases, 6z was revealed to be a focused MTKI that should have a bright future in fighting a wide range of cancers.

Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily, Axl regulates key processes such as cell growth, migration, aggregation, and apoptosis through several pathways. Its overexpression/overactivation has been underlined in several conditions, especially cancers, and in both chemotherapy and targeted therapy sensitivity loss. In this review, we propose to highlight the therapeutic implication of Axl, starting with the pathways it regulates, validating its interest as a therapeutic target, and defining the tools available to develop strategies for its inhibition. We especially focus on small molecule inhibitors, their structure, inhibition profile, and development stages.