Disintegrin and metalloproteinase domain-containing protein 9 (ADAM9)

Disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is a member of the ADAM family of transmembrane proteins, characterized by a multi-domain structure that includes both a metalloproteinase and a disintegrin domain [1][2]. It plays a pivotal role in the 'shedding' of various cell surface proteins, such as growth factors (e.g., pro-EGF), cytokines, and adhesion molecules, thereby modulating critical signaling pathways like EGFR and Notch [1][3]. While ADAM9 is involved in normal physiological processes such as wound healing and cell migration, its overexpression is strongly associated with the progression, invasion, and metastasis of several solid tumors, including lung, pancreatic, and breast cancers [2][4]. Due to its high expression on the surface of malignant cells compared to most healthy tissues, ADAM9 has become a significant target for antibody-drug conjugates (ADCs) like IMGC936, which aim to deliver potent cytotoxic payloads directly to tumor cells [5]. Beyond oncology, loss-of-function mutations in the ADAM9 gene are linked to autosomal recessive cone-rod dystrophy, highlighting its essential role in retinal maintenance [1][6]. [1] UniProt (Q13443); [2] PubMed (PMID: 33163157); [3] NCBI Gene (ID: 8754); [4] PubMed (PMID: 28651545); [5] ClinicalTrials.gov (NCT04622774); [6] PubMed (PMID: 19913470).

Other names

Metalloprotease/disintegrin/cysteine-rich protein 9MDC9Myeloma cell-derived protein 9Cell surface antigen MS7Cone-rod dystrophy 9

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic agents to ADAM9-expressing cells; inhibition of proteolytic activity and cell-surface protein shedding.