sgp130Fc

sgp130Fc, also known as sgp130-Fc or olamkicept, is a recombinant fusion protein designed to selectively inhibit interleukin-6 (IL-6) trans-signaling. It consists of the extracellular portion of the signal transduction receptor gp130 fused to the Fc region of human IgG1, producing a dimeric molecule with properties suitable for therapeutic use.

Mechanism of action: In IL-6 signaling, IL-6 binds to soluble IL-6 receptor (sIL-6R) to form a complex that can activate gp130 on cells lacking membrane IL-6R, a process called trans-signaling and associated with inflammation. sgp130Fc binds with high affinity to the IL-6/sIL-6R complex, preventing it from engaging gp130 on target cells. By sequestering this complex, sgp130Fc blocks trans-signaling while largely preserving classic signaling that uses membrane-bound IL-6R. This selectivity is intended to reduce inflammatory activity while maintaining normal IL-6–mediated homeostatic functions.

Development and status: sgp130Fc has been investigated in preclinical models and in early-phase clinical trials for inflammatory diseases driven by IL-6 trans-signaling, such as inflammatory bowel disease and rheumatoid arthritis. As of now, no regulatory approval has been granted, and development status has varied across programs and companies.

Structure and pharmacology: The Fc fusion provides dimerization and an extended circulatory half-life via Fc receptor recycling, supporting systemic administration in clinical settings. The approach represents a targeted strategy to dampen IL-6–related inflammation with the aim of reducing side effects associated with broader IL-6 blockade.

See also: Interleukin-6, IL-6 trans-signaling, gp130.