SNX-5422 (mesylate)

SNX-5422 Mesylate (PF-04929113 Mesylate), a prodrug of SNX-2112, is an orally active Hsp90 inhibitor, with a K_d of 41 nM, and also induces Her-2 degradation, with an IC₅₀ of 37 nM. IC50 & Target:IC50: 37 nM (Her-2)^[1]
Kd: 41 nM (Hsp90)^[1] In Vitro: SNX-5422 is an orally active Hsp90 inhibitor, with a K_d of 41 nM, and also induces Her-2 degradation, with an IC₅₀ of 37 nM. SNX-5422 exhibits potent effects on Her2 and p-ERK stability in AU565 cells and p-S6 in A375 cells, with IC₅₀s of 5 ± 1, 11 ± 3, and 61 ± 22 nM, respectively. SNX-5422 also induces Hsp70 in A375 cells with an IC₅₀ of 13 ± 3 nM^[1]. SNX-5422 (SNX5422; 0.5, 1, 2, 5, and 10 μM) reduces cell viability in a concentration-dependent manner. Moreover, SNX-5422 (1, 3, 5, 7 μM) in combination with equal amounts of HDAC inhibitors (PXD101, SAHA, and TSA) synergistically induces cell death via suppression of PI3K/Akt/mTOR signaling in ATC cells^[3]. In Vivo: SNX-5422 (50 mg/kg, p.o.) efficiently inhibits tumor growth of HT-29 human colon tumor xenograft model after administration 3 times a week for 3 weeks (qod × 3/2 × 3)^[1]. SNX-5422 (20, 40 mg/kg, p.o.) markedly inhibits multiple myeloma (MM) tumor growth and angiogenesis in mice^[2].