product name STF-62247
Description: STF-62247 shows selective toxicity and growth inhibition of renal cells lacking VHL; 25-fold greater sensitivity observed for cells with VHL deficiency compared to wild-type (VHL+). In vitro study demonstrated that STF-62247 exhibited selectively cytotoxicity and tumor growth inhibitory activity towards wild-type VHL and VHL-deficient renal cell carcinoma (RCC) in a HIF-independent manner with IC50 of 16 μM and 0.625 μM, respectively. In addion, STF-62247 also resulted in cell apoptosis by inducing acidification and increasing autophagy in VHL-deficient cells.
References: Cancer Cell. 2008 Jul 8;14(1):90-102; Cell Cycle. 2008 Oct;7(19):2987-90; Radiother Oncol. 2012 Jun;103(3):388-93.
267.35
Formula
C15H13N3S
CAS No.
315702-99-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 53 mg/mL (198.2 mM)
Water: <1 mg/mL
Ethanol: 3 mg/mL (11.2 mM)
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 7 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In vitro, STF-62247 shows cytotoxicity and tumor growth inhibitory activity against wild-type VHL and VHL-deficient renal cell carcinoma (RCC) in a HIF-independent manner with IC50 of 16 μM and 0.625 μM, respectively. Moreover, STF-62247 also leads to cell death by increasing acidification and inducing autophagy in VHL-deficient cells. STF-62247 specifically induces macroautophagy and enhances the fusion of autophagosome and lysosomes to form autolysosomes by interfering with Golgi-endoplasmic reticulum transport in cells that have lost VHL. A recent study shows that induction of autophagy by STF-62247 increases sensitivity of RCC under hypoxic conditions to radiation in a VHL-dependent manner. Kinase Assay: Cell Assay: For cell viability, 100,000 cells are plated in a 12-well plate. The following day, 1.25 μM STF-62247 is added in the presence or absence of 1 mM 3-MA for 24 hours at 37 °C. Cells are trypsinized and counted by trypan blue exclusion. For XTT assays, 5000 RCC4 with and without VHL cells or 2,500 SN12C with and without VHL shRNA cells are plated in 96-well plates. The following day, vehicle (DMSO), STF-62247 is added to media by serial dilution. Four days later, the media is aspirated and XTT solution containing 0.3 mg/ml of XTT in Phenol Red-free media, 20% FCS and 2.65 mg/ml N-methyl dibenzopyrazine methyl sulfate (PMS) is added to the cells and incubated at 37 °C for 1-2 hours. Metabolism of XTT is quantified by measuring the absorbance at 450 nm on a plate reader. |
|---|---|
| In Vivo | Animal experiments for STF-62247 activity were performed according to institutional and national guidelines and approved by Stanford Universitys Administrative Panel on Laboratory Animal Care. Based on an in vivo mouse model, it was found that intraperitoneal injection of STF-62247 at a dose of 8 mg/kg significantly inhibited tumor growth of VHL-deficient SN12C tumor cells. |
| Animal model | SN12C, SN12C-VHL shRNA or 786-O cells are injected subcutaneously into the flanks of immune-deficient mice. |
| Formulation & Dosage | Dissolved in DMSO and then diluted in water; ≤8 mg/kg; i.p. injection |
| References | Cancer Cell. 2008 Jul 8;14(1):90-102; Cell Cycle. 2008 Oct;7(19):2987-90; Radiother Oncol. 2012 Jun;103(3):388-93. |
