A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) (ADAM9)

A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is a membrane-anchored zinc-dependent metalloprotease belonging to the ADAM family (DIMA Biotechnology, 2024; PMC, 2020). It is characterized by a multi-domain structure that includes metalloproteinase, disintegrin, and cysteine-rich domains, allowing it to function in both ectodomain shedding and cell adhesion (PMC, 2020; Patsnap, 2024). ADAM9 cleaves various cell surface molecules, including growth factors like HB-EGF and adhesion molecules, thereby regulating signaling pathways such as EGFR/AKT that drive cell proliferation and survival (PMC, 2014; PMC, 2022). In many cancers, including lung, breast, and prostate, ADAM9 is overexpressed and correlates with increased metastasis and poor prognosis (DIMA Biotechnology, 2024; Atlas of Genetics, 2009; PMC, 2020). This high expression on tumor cells makes it an attractive target for antibody-drug conjugates (ADCs), such as IMGC-936 and MGC-028, which utilize ADAM9-specific antibodies to deliver potent cytotoxic payloads directly to malignant cells (DIMA Biotechnology, 2024; Patsnap, 2024). However, the development of ADAM9-targeted therapies must account for its broad expression in healthy tissues and its critical role in the retina, where its absence is linked to cone-rod dystrophy (UniProt, 2024).

Other names

MDC9Meltrin-gammaCellular disintegrin-related proteinMyeloma cell metalloproteinaseMetalloproteinase/disintegrin/cysteine-rich protein 9Cone-rod dystrophy 9 (CORD9)

Antibody-drug conjugate (ADC) targeting ADAM9 to deliver cytotoxic payloads (e.g., maytansinoids or exatecan derivatives) to ADAM9-expressing cells (DIMA Biotechnology, 2024; Patsnap, 2024); inhibition of proteolytic activity and cell adhesion (Patsnap, 2024).