ADAM17 Inhibitor

GW280264X is the mixed ADAM10/TACE (ADAM17) metalloproteinases inhibitor. GW280264X potently blocks TACE (ADAM17) and ADAM10 with IC₅₀s of 8.0 nM and 11.5 nM, respectively. ADAM10 and 17 modulate the immunogenicity of glioblastoma-initiating cells.

TAPI-1 is a broad-spectrum MMP inhibitor and NF-κB p65 inhibitor that targets ADAM17/TACE, ADAM10 and other proteins. TAPI-1 reduces the proteolytic cleavage of membrane-bound TNF-α, decreases TNF-α levels, inhibits NF-κB pathway activation, and downregulates profibrotic markers. TAPI-1 reduces the proportion of proinflammatory immune cells, alleviates cardiac and airway fibrosis, and improves cardiac function after myocardial infarction. Meanwhile, TAPI-1 inhibits the viability, migration and invasion of esophageal squamous cell carcinoma cells, enhances the chemosensitivity of Cisplatin (HY-17394), induces apoptosis, and shows low toxicity to normal esophageal epithelial cells. TAPI-1 can be widely used in studies related to myocardial infarction-induced heart failure, severe traumatic tracheal stenosis, esophageal squamous cell carcinoma and other conditions.

KP-457 is a selective a disintegrin and metalloproteinase 17 (ADAM17) inhibitor, with higher selectivity for ADAM17 than for other MMPs and ADAM10, and IC₅₀s are 11.1 nM (ADAM17), 748 nM (ADAM10), 717 nM (MMP2), 9760 nM (MMP3), 2200 nM (MMP8), 5410 nM (MMP9), 930 nM (MMP13), 2140 nM (MMP14), and 7100 nM (MMP17), respectively.

Aderbasib (INCB007839) is a potent, orally active and target specific low nanomolar hydroxamate-based inhibitor of ADAM10 and ADAM17. Aderbasib exhibits robust antineoplastic activity and can be used for cancer research, including diffuse large B-cell non-Hodgkin lymphoma, HER2⁺ breast cancer, gliomas, et al.

JG26 is an ADAM inhibitor with IC₅₀ values of 12 nM, 1.9 nM, and 150 nM for ADAM8, ADAM17, and ADAM10, respectively. JG26 inhibits MMP-12 with an IC₅₀ value of 9.4 nM. JG26 inhibits AngII (HY-13948)-induced EGFR transactivation and ERK activation. JG26 increases the expression of ACE2, inhibits the cleavage of CD23, reduces the infection of SARS-CoV-2. JG26 inhibits colorectal cancer metastasis. JG26 can be used for research on Hodgkin lymphoma and vascular diseases.

D8P1C1 is a high-affinity ADAM17 inhibitor (with a K_d of 180 pM targeting ADAM17-ECD) that reduces the shedding and phosphorylation of EGFR ligands. D8P1C1 inhibits cancer cell proliferation in vitro and tumor growth in xenograft models. ⁸⁹Zr-DFO-D8P1C1 radioimmunological PET imaging shows its substantial accumulation in ovarian tumor xenografts, serving as a platform for generating bispecific T-cell engager derivatives. D8P1C1 can be applied to research on related diseases including triple-negative breast cancer, various types of ovarian cancer, lung adenocarcinoma, glioma, and colon cancer.

MEDI-3622 is a human monoclonal antibody against ADAM17. MEDI-3622 blocks the ADAM17-mediated shedding of CD16A and CD62L on NK cells, and binds with high specificity to a surface loop unique to the metalloprotease catalytic domain of ADAM17. MEDI-3622 enhances IFNγ production by NK cells when they bind to antibody-coated tumor cells. MEDI-3622 can be used in the research of ovarian cancer, Burkitt lymphoma, head and neck cancer, and colorectal cancer.

ADAM17-IN-1 is a selective inhibitor of ADAM17. ADAM17-IN-1 inhibits ADAM17 activity to reduce metabolic activity of dendritic cells (DCs), impair DC antigen-presenting function, suppress allergen-specific Th2 cell polarization, and reduce Th2 cytokine (IL-4, IL-5, IL-13) secretion. ADAM17-IN-1 demonstrates protective efficacy against house dust mite (HDM)-induced type 2/eosinophilic airway inflammation in mice. ADAM17-IN-1 can be used for the study of type 2-high allergic asthma.