Background:

IC50: 0.02, 0.03, 0.51 and >100 μM for VEGFR2, FGFR1, PDGFRβ and EGFR, respectively

SU 5402 is an inhibitor of VEGF, FGF, and PDGF receptor tyrosine kinases. Receptor tyrosine kinases have been recognized as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, and cardiovascular diseases.

In vitro: SU5402 could inhibit FGFR3 phosphorylation in vitro. B cells dependent on FGFR3 for survival were sensitive to SU5402 specifically. A panel of 11 human myeloma cell lines was studied, among which five beared t(4;14) translocation. The KMS11 human myeloma cell line expressesing constitutively active mutant FGFR3, displayed a 95% increase in G0/G1 cells as well as 45-fold increase in apoptotic cells after SU5402 treatment. In addition, the activated signal-regulated kinases 1 and 2 and signal activator of transcription 3 were down-regulated after SU5402 treatment rapidly. In human myeloma cell lines with wild-type FGFR3, the stimulating effect of aFGF ligand was abrogated by SU5402 [1].

In vivo: BALB/c mice were inoculated with syngeneic pre-B-TD cells and these established tumours were treated with 300 ng/kg SU5402 or carrier alone administered by either direct subcutaneous or intraperitoneal injection. Tumours were collected 24 h later and Western blot analyses indicated a treatment-related decrease in the levels of activated ERK1/2 in the harvested tumors [1].

Clinical trial: N/A

Reference:
[1] Paterson JL,Li Z,Wen XY,Masih-Khan E,Chang H,Pollett JB,Trudel S,Stewart AK.  Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma. Br J Haematol.2004 Mar;124(5):595-603.