Preparation of Site-Specific Cytotoxic Protein Conjugates via Maleimide-thiol Chemistry and Sortase A-Mediated Ligation

Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model

“…Previously, we have shown that fibroblast growth factors 1 and 2 (FGF1 and FGF2) are suitable targeting molecules for killing cancer cells overproducing fibroblast growth factor receptor 1 (FGFR1). 9 − 17 FGFR1 is a transmembrane protein that plays a substantial role in regulating cell proliferation, survival, differentiation, migration, and angiogenesis. 18 − 23 Analyses have shown that 7.1% of all cancer types are associated with aberration of the FGF-FGFR pathway, with FGFR1 being the most commonly affected.…”

“…Previously, we have shown that fibroblast growth factors 1 and 2 (FGF1 and FGF2) are suitable targeting molecules for killing cancer cells overproducing fibroblast growth factor receptor 1 (FGFR1). − FGFR1 is a transmembrane protein that plays a substantial role in regulating cell proliferation, survival, differentiation, migration, and angiogenesis. − Analyses have shown that 7.1% of all cancer types are associated with aberration of the FGF-FGFR pathway, with FGFR1 being the most commonly affected. , Upregulation of FGFR1 occurs in many types of tumors, including bladder, breast, lungs, multiple myeloma, pancreatic, prostate, and various sarcomas. ,,− Furthermore, overexpression of FGFR1 is correlated with poor prognosis. , Thus, the development of therapy based on FGF2 conjugates targeting FGFR1 is most warranted. FGF2, however, is a relatively small protein (17.2 kDa), which does not have adequate pharmacokinetic properties.…”