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CH5183284 (Debio-1347) is a selective and novel inhibitor of FGFR with IC50 value of 9.3, 7.6, 22 and 290 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively [1].

Fibroblast growth factor receptors (FGFRs) are tyrosine kinases and receptors for fibroblast growth factors and consist of FGFR1, FGFR2, FGFR3 and FGFR4. In cancer, FGFR is activated by point mutations, gene amplification or chromosomal translocations/rearrangements and is involved in angiogenesis, cell growth, cell migration, invasion and metastasis [1].

CH5183284 (Debio-1347) is a selective and novel FGFR inhibitor. In a competitive binding assay, CH5183284 (Debio-1347) binding with FGFR1, FGFR2, FGFR3, FGFR4 and KDR with Kd values of 20, 20, 25, 740 and 960 nM, respectively. In DMS114, SNU-16 and KMS11 cell lines, CH5183284 (Debio-1347) (100-300 nM) inhibited autophosphorylation of FGFR1, FGFR2 and FGFR3. In cancer cell lines with the FGFR genetic alterations, CH5183284 (Debio-1347) showed antiproliferative activity [1].

In xenograft mouse models, CH5183284 (Debio-1347) inhibited tumor growth against xenografts with FGFR genetic alterations such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE-280 (endometrial cancer, FGFR2 S252W mutation), SNU-16 (gastric cancer, FGFR2 amplification), RT112/84 (bladder cancer, FGFR3-TACC3 fusion) and UM-UC-14 (bladder cancer, FGFR3 S249C mutation) by 134%, 100%, 147%, 125% and 116%, respectively [1].

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