TMI 1 (CAS 287403-39-8) is a potent dual inhibitor of ADAM17 (TACE) and matrix metalloproteases, also known as WAY-171318 and PF-05312062. The compound demonstrates nanomolar inhibitory activity across multiple metalloprotease targets and is orally bioavailable, making it a versatile tool for inflammation and oncology research. Enamine offers TMI 1 as a high-purity screening sample for in vitro and in vivo experimental models.
TMI 1 is a hydroxamate-based thiomorpholine compound with molecular formula C₁₇H₂₂N₂O₅S₂ and TMI 1 molecular weight of 398.49 g/mol. The TMI 1 chemical structure incorporates a sulfonyl-linked phenyl group with a butynyloxy substituent and an N-hydroxy carboxamide moiety responsible for zinc ion coordination at the active site. Researchers study the TMI 1 structure to understand its binding geometry within MMP and ADAM17 catalytic domains. The compound is registered under CAS 287403-39-8 and sold under agreement from Pfizer Inc.
Application of TMI 1
TMI 1 is applied in research targeting TNF-α–driven inflammatory pathways, metalloprotease-mediated tissue remodeling, and tumor biology. It is particularly relevant for studies on rheumatoid arthritis, cancer progression, and neuroinflammation. WAY-171318 is used in screening workflows requiring well-characterized reference inhibitors and in mechanistic studies exploring ADAM17 substrate shedding and downstream cytokine regulation.
In Vitro
TMI 1 inhibits ADAM17 and a broad panel of MMPs with IC₅₀ values of 3–26 nM across MMP-13, MMP-2, MMP-1, ADAM17, MMP-9, MMP-7, and MMP-14. The compound potently suppresses LPS-induced TNF-α secretion in human primary monocytes and whole blood, and selectively induces caspase-dependent apoptosis in triple-negative and ERBB2-overexpressing breast tumor cell lines.
In Vivo
In vivo, TMI 1 suppresses TNF-α production in an acute LPS mouse model and reduces severity scores in a rheumatoid arthritis model. PF-05312062 induces tumor apoptosis in a breast cancer model and demonstrates oral bioavailability, supporting its use in dose-response and translational research studies.
Biochemical and Physiological Actions
TMI 1 acts by coordinating the catalytic zinc ion within the ADAM17 and MMP active sites through its hydroxamate moiety, blocking substrate access and proteolytic processing. This reduces ectodomain shedding of TNF-α and attenuates downstream inflammatory signaling. At the cellular level, WAY-171318 triggers caspase-dependent apoptosis selectively in tumor cells, with limited toxicity toward normal cells.
Features and Benefits of TMI 1
TMI 1 (WAY-171318, CAS 287403-39-8) offers a well-documented activity profile across multiple research areas:
- nanomolar potency against ADAM17 and a broad MMP panel with defined IC₅₀ values;
- selective tumor cell cytotoxicity via caspase-dependent apoptosis;
- oral bioavailability supporting in vitro and in vivo experimental designs;
- validated reference compound licensed from Pfizer.
When sourced as EBC-114027, TMI 1 is provided with analytical quality control data for consistent use in pharmacological and biochemical studies.
