VER-50589

VER-50589 is a Hsp90 inhibitor, with an IC50 of 21 nM and a Kd of 4.5 nM.

Research Areas >> Cancer

HSP90:21 nM (IC50)

VER-50589 is a Hsp90 inhibitor, with an IC50 of 21 nM and a Kd of 4.5 nM. VER-50589 inhibits intrinsic ATPase of full-length recombinant yeast Hsp90, with an IC50 of 143 ± 23 nM in the presence of 400 μM ATP. VER-50589 shows antiproliferative activities against various human cancer cells, with the lowest GI50 of 32.7 ± 0.2 nM for CH1 human ovarian cells, and mean GI50 of 78 ± 15 nM. VER-50589 suppressses the proliferation of human umbilical vein endothelial cells (HUVEC) with GI50 value of 19 ± 2.4 nM, and shows higher GI50s against nontumorigenic human breast (MCF10a) and prostate (PNT2) epithelial cells. Furthermore, VER-50589 displays no differences in cellular activities of isogenic cell lines, and these activities are independent of NQO1 expression. VER-50589 also causes G1 and G2-M block (115 or 575 nM) and induces cytostasis in HCT116 colon cancer cells. In addition, VER-50589 causes great uptake in HCT116 cells[1].

VER-50589 (4 mg/kg, i.p.) exerts a complete HSP90 inhibition in the athymic mice bearing well-established OVCAR3 human ovarian ascites tumors. VER-50589 (100 mg/kg, i.p.) shows reduced tumor volume and tumor weights in the HCT116 colon carcinoma xenografts compared to the control mice group[1].

HCT116 and HT29 human colon cancer cells are seeded and left to attach overnight. Vehicle control or compound (VER-50589) is added for 1, 4, and 24 h. Attached cells are collected and counted by hemacytometer. Incubation medium (1 mL) and cell pellets are frozen at −80°C until mass spectrometry analysis[1].

HCT116 cells (2-5 million cells per site) are injected s.c. in the flanks of 6- to 8-week-old female NCr athymic mice. Dosing commenced when tumors are well established (∼5-6 mm diameter). For combined therapy and pharmacokinetic and pharmacodynamic studies, mice bearing HCT116 xenografts are administered 100 mg/kg VER-50589 i.p. per day for 9 days. Tumor volumes are calculated. On study termination, blood samples are taken, and plasma is separated and stored −80°C. Tumors are excised, weighed, and snap frozen at −80°C[1].

[1]. Sharp SY, et al. Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues. Mol Cancer Ther. 2007 Apr;6(4):1198-211.

17-AAG | Ganetespib(STA-9090) | NVP-AUY922 | Geldanamycin | VER-155008 | AT13387 | 17-DMAG (Alvespimycin) HCl | BIIB021 | Apoptozole | IPI-504 | KNK437 | Teprenone | KRIBB11 | Debio-0932 | HSP-990