TMI-2

TMI-2 is a highly specific small molecule inhibitor of Tumor Necrosis Factor-alpha Converting Enzyme (TACE), also known as ADAM17 (A Disintegrin and Metalloproteinase domain-containing protein 17). Originally developed by Wyeth (now Pfizer) as part of a series of thiomorpholine sulfonamide hydroxamates, TMI-2 was designed to block the proteolytic cleavage and release of soluble TNF-α and other membrane-bound proteins. Recent research, including studies presented at AACR 2026, indicates that TMI-2 can overcome resistance to immune checkpoint blockade (ICB) therapy. By inhibiting ADAM17 activity, TMI-2 modulates the immune cell infiltrate within the tumor microenvironment—specifically affecting myeloid and T cell populations—and reduces TNF-α-induced cell death in certain immune subsets. TMI-2 has demonstrated a favorable safety profile in humans and is being investigated as a sensitizing agent for ICB-resistant cancers, such as squamous cell carcinoma.

Other names

TACE inhibitor TMI-2ADAM17 inhibitor TMI-2ADAM-17 inhibitor TMI-2ADAM 17 inhibitor TMI-2