Background:

PD173074 is a poten and selective fibroblast growth factor receptor (FGFR) inhibitor. Fibroblast growth factor-2 is reported to be able to induce proliferation and chemoresistance in Small cell lung cancer (SCLC) cells.

In vitro: PD173074 was found to block H-510 and H-69 SCLC proliferation and clonogenic growth in a dose-dependent fashion and prevent FGF-2-induced chemoresistance as well. These effects correlate with the inhibition of both FGFR1 and FGFR2 transphosphorylation. In addition, PD173074 showed a high degree of selectivity for FGFR tyrosine kinase [2].

In vivo: In the H-510 xenograft mouse model, tumor growth was significanlty improved similar to that seen with single-agent cisplatin administration. Accordingly, PD173074 treatment resulted in significanlty prolonged median survival when compared with that of control sham-treated animals. More dramatically, PD173074 also induced complete responses lasting >6 months in 50% of in mice H-69 xenografts [2].

Clinical trial: PD173074 is still in the preclinical development stage, and no clinical data are available currently.

参考文献:
[1] Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, Lemoine NR, Stamp GW, Aboagye EO, Seckl MJ.  The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res. 2009 Nov 15;69(22):8645-51.
[2] Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR.  Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998 Oct 15;17(20):5896-904.