SNX-2112

SNX-2112 (PF 04928473) is an orally active Hsp90 inhibitor, with a K_d of 16 nM for Hsp90 and IC₅₀s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC₅₀s of 10 nM, 4.275 μM and 0.862 μM, respectively^[1]. SNX-2112 (PF 04928473) binds Hsp90 isoforms Hsp90α, Hsp90β and Hsp90b1/Grp94 with K_ds of 4 nM, 6 nM and 484 nM, respectively^[2]. IC50 & Target:IC50: 10 nM (Her-2)^[1], 30 nM (Hsp90 α), 30 nM (Hsp90 β), 4.275 μM (Grp94), 0.862 μM (Trap-1)^[2]
Kd: 16 nM (Hsp90)^[1] In Vitro: SNX-2112 is an orally active Hsp90 inhibitor, with a K_d of 16 nM, and also induces Her-2 degradation, with an IC₅₀ of 10 nM^[3]. SNX-2112 binds to Hsp90, with IC₅₀s of 30 nM, 30 nM, 4.275 μM and 0.862 μM for Hsp90 α and β, Grp94 and Trap-1, respectively^[1]. SNX-2112 shows potent antiproliferative activity against various cancer cell types, with IC₅₀s of 3 nM to 53 nM. SNX-2112 exhibits potent effects on Her2 and p-ERK stability in AU565 cells and p-S6 in A375 cells, with IC₅₀s of 11 ± 5, 41 ± 12, and 1 ± 0.6 nM, respectively. SNX-2112 also induces Hsp70 in A375 cells with an IC₅₀ of 2 ± 0.9 nM^[3]. In addition, SNX-2112 potently blocks signaling of Hsp90 clients, such as Akt, ERK, and NF-κB pathways in different cells. SNX-2112 inhibits multiple myeloma (MM) cell growth, including MM.1S, U266, INA-6, RPMI8226, OPM1, OPM2, MM.1R, and Dox40 MM cell lines, with IC₅₀s of 52, 55, 19, 186, 89, 67, 93, and 53 nM at 48 hours, respectively. SNX-2112 (2.5-10 nM) also suppresses osteoclast formation, associated with down-regulation of ERK/c-fos and PU.1^[4].