ADAM17-IN-1 is a selective ADAM17 inhibitor. It functions by reducing dendritic cell (DC) metabolic activity through ADAM17 inhibition, thereby impairing DC antigen presentation, suppressing allergen-specific Th2 cell polarization, and decreasing the secretion of Th2 cytokines (IL-4, IL-5, IL-13). In mouse models of house dust mite (HDM)-induced type 2/eosinophilic airway inflammation, ADAM17-IN-1 demonstrates protective effects. This compound can be utilized in research on type 2 hyperreactive allergic asthma.

ADAM17-IN-1 (Compound 2155-17) at a concentration of 50 μM significantly reduces the oxygen consumption rate (OCR) and spare respiratory capacity (SRC) of bone marrow-derived dendritic cells (BMDCs), inhibits mitochondrial oxidative phosphorylation, and impairs the metabolic activity of dendritic cells. When pre-treated at 50 μM in HDM-stimulated BMDCs, followed by co-culturing with CFSE-labeled CD4+ T cells from OTII mice for four days, ADAM17-IN-1 markedly diminishes the proliferation rate of OVA 323-339 peptide-specific T cells, reduces Th2 cytokine (IL-13) secretion, and lowers the proportion of CD4+ GATA3+ Th2 cells. Additionally, ADAM17-IN-1, in a concentration range of 0.316-3.16 μM, promotes the differentiation of mouse oligodendrocyte progenitor cells (OPCs) in a dose-dependent manner without inducing apoptosis or showing notable cytotoxicity.

ADAM17-IN-1 (Compound 2155-17) at an in vitro pretreatment concentration of 50 μM for 16 hours, administered intranasally with 0.75×10^5 CD11c+ BMDCs on day 0, followed by HDM challenges on days 9, 11, 13, and 15 (50 μg per mouse), significantly reduces eosinophil numbers in both BAL and lung tissues. Furthermore, ADAM17-IN-1 (200 μg per mouse, intranasal administration, on days 8, 10, 12, and 14 concurrent with HDM stimulation) markedly decreases the total inflammatory cells and eosinophils in BAL/lung.