STF-62247

• CAT Number: I003123
• CAS Number: 315702-99-9
• Molecular Formula: C15H13N3S
• Molecular Weight: 267.3
• Purity: ≥95%
• Synonyms: N-(3-methylphenyl)-4-pyridin-4-yl-1,3-thiazol-2-amine
• Target: Autophagy
• Solubility: DMSO: ≥ 31 mg/mL
• Storage: 3 years -20C powder
• InChIKey: KATNUHQNJGNLPW-UHFFFAOYSA-N

STF-62247 is TGN inhibitor with IC50 of 0.625μM and 16μM in RCC4 and RCC4/VHL cells,respectively.It specifically induces autophagic cell death in cells that have lost VHL, an essential mutation in the development of RCC.IC50: 0.625/16μM in RCC4 and RCC4/VHL cells,respectively.[1]In vitro: STF-62247 induces cytotoxicity in VHL-deficient cells in a HIF-independent manner, STF-62247 increases acidification in VHL-deficient cells ,TGN is a target of STF-62247 and a drug-selective pathway synthetically lethal in VHL-deficient cells.[1] Golgi trafficking are required as initial signals in STF-62247-induced autophagy.[2]STF-62247 increases radiosensitivity in a VHL-dependent manner.[3]In vivo: SN12C, SN12C-VHL shRNA, or 786-O cells were implanted subcutaneously into the flanks of immunodeficient mice. The selective cytotoxicity of STF-62247 for the VHL-deficient cells was also demonstrated in 786-O cells compared to their wild-type VHL counterparts by clonogenic assay in vitro. Daily treatment with STF-62247 significantly reduced tumor growth of VHL-deficient cells. This decrease in tumor growth was concentration dependent. Importantly, drug treatment did not have any effect on the growth of SN12C tumor cells that have wild-type VHL. Together,STF-62247 reduces tumor growth in VHL-deficient cells in mice.[1]

Reference

[1]. Turcotte, S. et al. A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy. Cancer cell 14, 90-102, doi:10.1016/j.ccr.2008.06.004 (2008)

[2]. Chan, D. A. & Giaccia, A. J. Targeting cancer cells by synthetic lethality: autophagy and VHL in cancer therapeutics. Cell cycle 7, 2987-2990, doi:10.4161/cc.7.19.6776 (2008)

[3]. Anbalagan, S. et al. Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 103, 388-393, doi:10.1016/j.radonc.2012.04.001 (2012