Luminespib (mesylate)

Luminespib mesylate (VER-52296 mesylate) is a potent HSP90 inhibitor with IC₅₀s of 7.8 and 21 nM for HSP90α and HSP90β, respectively^[1]. IC50 & Target:IC50: 7.8 nM (HSP90α), 21 nM (HSP90β), 535 nM (GRP94), 85 nM (TRAP-1)^[1] In Vitro:Luminespib mesylate (VER-52296 mesylate) is a potent and selective HSP90 inhibitor, with IC₅₀s and K_is of 21 ± 16, 8.2 ± 0.7 nM against HSP90β and of 7.8 ± 1.8, 9.0 ± 5.0 nM for HSP90α^[1].
Luminespib mesylate shows weak activity against GRP94 and TRAP-1 wich IC₅₀s of 535 ± 51 nM (K_i, 108 nM) and 85 ± 8 nM (K_i, 53 nM), respectively^[1].
Luminespib mesylate exhibits inhibitory effect on proliferation of various human tumor cell lines (2.3-49.6 nM), induces cell cycle arrest and apoptosis and depletes client proteins in human cancer cells (80 nM)^[1].
Luminespib (100 nM) mesylate significantly reduces CD40L fibroblast-induced changes in immunophenotype and STAT3 signaling but with no effect on the viability of chronic lymphocytic leukemia (CLL) cells^[2].
Luminespib (500 nM) mesylate in combination with NSC 118218 (Fludarabine) (HY-B0069) more effectively induces apoptosis in cells in co-culture than either drug alone, and overcomes fibroblast-derived resistance to Hsp90 inhibitor^[2].
Luminespib mesylate shows great inhibition of pancreatic cancer cells with IC₅₀ of at 10 nM^[3].
Luminespib (10 nM) mesylate reduces the expression and the epidermal growth factor (EGF)-mediated activation of EGFR and substantially disrupts EGF signaling in terms of diminishing downstream phosphorylation of ERK^{Thr202/Tyr204[3]}.
Luminespib (10 nM) mesylate significantly blocks pancreatic cancer cell migration and invasion both in the absence and presence of EGF^[3].
In Vivo:Luminespib (50, 75 mg/kg, i.p.) mesylate (VER-52296 mesylate) significantly inhibits tumor growth rate, reducing the mean weights of tumors on day 11 in human tumor xenografts^[2].
Luminespib (50 mg/kg/week, 3×25 mg/kg/week) mesylate significantly reduces tumor growth rates and lowers tumor weights in the L3.6pl pancreatic cancer cell-bearing mice model^[3].