Inducible fibroblast growth factor receptor 1 fusion protein (iFGFR1) (iFGFR1)

The Inducible fibroblast growth factor receptor 1 (iFGFR1) fusion protein is an engineered signaling molecule designed to provide precise, drug-dependent control over the FGFR1 pathway (Welm et al., 2002). It consists of the intracellular kinase domain of the fibroblast growth factor receptor 1 fused to one or more FK506-binding protein (FKBP12) domains containing a specific F36V mutation (Clackson et al., 1998). This mutation creates a unique hydrophobic pocket that selectively binds synthetic dimerizing agents, such as rimiducid (AP1903) or AP20187, while avoiding interaction with endogenous wild-type FKBP12. Upon administration of the dimerizer, the fusion proteins are cross-linked, mimicking the natural ligand-induced dimerization of FGFR1 and triggering downstream signaling cascades, including the MAPK/ERK and PI3K/Akt pathways (Freeman et al., 2003). In clinical applications, particularly adoptive cell therapies like CAR-T, iFGFR1 is utilized as a "proliferation switch" to drive the expansion and survival of engineered cells in vivo (Bell et al., 2016). This system allows clinicians to enhance the therapeutic window and persistence of cell-based medicines through the controlled administration of a small-molecule drug.

Other names

iFGFR1FKBP-FGFR1Inducible FGFR1FKBPF36V-FGFR1 fusion proteinFKBP12(F36V)-FGFR1AP20187-inducible FGFR1

The small-molecule dimerizer (e.g., rimiducid) acts as a chemical inducer of dimerization (CID) by binding to the FKBPF36V domains, which brings the fused FGFR1 kinase domains into proximity, leading to trans-phosphorylation and activation of downstream signaling pathways such as MAPK/ERK and PI3K/Akt (Welm et al., 2002; Bell et al., 2016).