Uses
NVP-HSP990 is an orally available HSP90 inhibitor.
Biological Activity
hsp990 (nvp-hsp990) is a potent and selective inhibitor of hsp90 with ic50 values of 0.6, 0.8 and 8.5 nm for hsp90α, hsp90β and grp94, respectively [1].heat shock protein 90 (hsp90) is a chaperone protein that stabilizes proteins against heat stress, assists proteins to fold properly and aids in protein degradation. also, hsp90 stabilizes proteins required for tumor growth.hsp990 (nvp-hsp990) is a potent and selective hsp90 inhibitor. nvp-hsp990 bound to the n-terminal atp-binding domain of hsp90. nvp-hsp990 inhibited trap1 atpase activity by 90% with ic50 value of 320 nm. in gtl-16 cells, nvp-hsp990 destabilized the hsp90-p23 complex in a concentration- and time-dependent way. also, nvp-hsp990 decreased c-met with ec50 value of 37 nm and induced hsp70 with ec50 value of 20 nm. nvp-hsp990 inhibited erk and akt phosphorylation with ec50 values of 11 and 6 nm respectively and thus inhibited erk and akt activation. in five human tumor cell lines, nvp-hsp990 inhibited cell growth with gi50 values of 4-40 nm [1]. in glioma tumor-initiating cells, nvp-hsp990 inhibited cell growth with ic50 value of 10-500 nm in a dose-dependent way and reduced cdk2 and cdk4, thus disrupting cell-cycle control [2].in the gtl-16 gastric cancer mice model, nvp-hsp990 exhibited antitumor efficacy [1].
References
[1]. menezes dl, taverna p, jensen mr, et al. the novel oral hsp90 inhibitor nvp-hsp990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. mol cancer ther, 2012, 11(3): 730-739.
[2]. fu j, koul d, yao j, et al. novel hsp90 inhibitor nvp-hsp990 targets cell-cycle regulators to ablate olig2-positive glioma tumor-initiating cells. cancer res, 2013, 73(10): 3062-3074.
