Background:

PF-04929113 is an inhibitor of Hsp90 [1].

PF-04929113 is a water-soluble and oral pre-PF-04928473, which can be rapidly absorbed and converted into PF-04928473 after oral administration. In BT-474 xenograft mice, PF-04928473 induced the degradation of HER2 client protein. No obvious toxicity was observed when the dose reached 150mg/kg. PF-04928473 at 100mg/kg resulted in complete tumor growth inhibition and local tumor regression in some mice. In H1650 xenograft mice, PF-04928473 also showed significant anti-tumor activity. In addition, as an inhibitor of Hsp90, PF-04928473 inhibits p-ERK and p-Akt in vivo, reduces CD31+ cells and MVD, and has an effect on angiogenesis [1,2].

参考文献:
[1] Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8.
[2] Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55.