product name VER-50589
Description: VER-50589 is a novel, highly potent and selective HSP90 inhibitor with IC50 of 21 nM for HSP90β. It produces a mean cellular antiproliferative GI50 value of 78 nM when tested against a human cancer cell line panel. VER-50589 shows favorable pharmacokinetics and impairs tumor growth in animals. VER-50589 inhibited recombinant yeast Hsp90 ATPase activity with IC50 value of 143 nM at 400 μM ATP and inhibited recombinant human HSP90β with IC50 value of 821 nM in the presence of the activator AHA1. Also, VER-50589 bound to recombinant human HSP90β with Kd value of 4.5 nM.
References: Mol Cancer Ther. 2007 Apr;6(4):1198-211.
388.80
Formula
C19H17ClN2O5
CAS No.
747413-08-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 77 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: 77 mg/mL (198.0 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: VER-50589 inhibits the intrinsic ATPase activity of recombinant yeast Hsp90 with IC50 of 143 nM, and produces antiproliferative activity in a panel of human cancer cell lines and nontumorigenic cells in vitro. VER-50589 causes induction of HSP72 and HSP27 alongside depletion of client proteins, including C-RAF, B-RAF, and survivin, and the protein arginine methyltransferase PRMT5, which further result in cell cycle arrest and apoptosis. Kinase Assay: Binding of HSP90 inhibitors to human full-length recombinant HSP90β is determined by a competitive binding fluorescence polarization assay, using a fluorescent pyrazole resorcinol probe. Cell Assay: Antiproliferative effects are measured using the sulforhodamine B assay. HUVEC sensitivity is determined by an alkaline phosphatase method. Cells: Melanoma cells (SKMEL 2, SKMEL 5, SKMEL 28, WM266.4); Colon cancer cells (HCT116, BEneg, BE2, HT29, HT29oxaliR); Ovarian cancer cells (CH1, CH1doxR); Breast cancer cells (MB-231, MB-468, BT20, ZR751, MCF7, BT-474); nontumorigenic cells (HUVEC, MCF10a, PNT) |
|---|---|
| In Vivo | In HCT116 human colon cancer xenografts, VER-50589 (100 mg/kg i.p.) results in a statistically significant reduction of ∼30% in tumor volume and weight, as well as induction of HSP72 and depletion of ERBB2 and C-RAF. |
| Animal model | HCT116 human colon cancer xenografts |
| Formulation & Dosage | Dissolved in 10% DMSO, 5% Tween 20, 85% saline; 100 mg/kg; i.p. injection |
| References | Mol Cancer Ther. 2007 Apr;6(4):1198-211. |
