product name VER-49009
Description: VER-49009 (also known as CCT0129397) is a potent and selective HSP90 inhibitor with IC50 of 47 nM for HSP90β. VER-49009 produces a cellular antiproliferative GI50 value of 685 nM when tested against a human cancer cell line panel. Consistent with inhibition of Hsp90, VER-49009 induces the expression of Hsp27 and Hsp72 while reducing the client proteins C-RAF, B-RAF, survivin, and PRMT5, causing cell cycle arrest and apoptosis.
References: Mol Cancer Ther. 2007 Apr;6(4):1198-211; Mol Cell Biochem. 2009 Oct;330(1-2):181-5.
387.82
Formula
C19H18ClN3O4
CAS No.
558640-51-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 77 mg/mL (198.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
CCT0129397
other peoduct :
| In Vitro |
In vitro activity: VER-49009 inhibits the intrinsic ATPase activity of recombinant yeast Hsp90 with IC50 of 167 nM, and produces antiproliferative activity in a panel of human cancer cell lines and nontumorigenic cells in vitro. VER-49009 causes induction of HSP72 and HSP27 with depletion of client proteins, including C-RAF, B-RAF, and survivin, and PRMT5, which further result in cell cycle arrest and apoptosis. VER-49009 inhibits the cell proliferation, and induces G2 phase arrest in hepatic stellate cell line CFSC cells, which may suggest a rational approach in the prevention of liver fibrosis. 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 athymic mice, VER-49009 (20 mg/kg, i.v.) shows rapid clearance with values of 0.187 L/h. In an orthotopic human ovarian carcinoma model, VER-49009 (4 mg/kg, i.p.) also induces the depletion of the sensitive HSP90 client protein ERBB2. |
| Animal model | Mice bearing established OVCAR3 human ovarian xenografts. |
| Formulation & Dosage | Dissolved in 10% DMSO, 5% Tween 20, 85% saline; 4 mg/kg; i.p. injection |
| References | Mol Cancer Ther. 2007 Apr;6(4):1198-211; Mol Cell Biochem. 2009 Oct;330(1-2):181-5. |
