STF-62247

Names

[ Name ]:
STF-62247

[Synonym ]:
STF-62247
2-Thiazolamine, N-(3-methylphenyl)-4-(4-pyridinyl)-
N-(3-Methylphenyl)-4-(4-pyridinyl)-1,3-thiazol-2-amine
N-(3-methyl-phenyl)-4-pyridin-4-yl-1,3-thiazol-2-amine
4-(pyridin-4-yl)-N-m-tolylthiazol-2-amine
N-(3-Methylphenyl)-4-(4-pyridinyl)-2-thiazolamine
S1041_Selleck

Biological Activity

[Description]:

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]

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

[References]

[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

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
444.8±47.0 °C at 760 mmHg

[ Melting Point ]:
174.66° C

[ Molecular Formula ]:
C₁₅H₁₃N₃S

[ Molecular Weight ]:
267.349

[ Flash Point ]:
222.8±29.3 °C

[ Exact Mass ]:
267.083008

[ PSA ]:
66.05000

[ LogP ]:
3.16

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.671

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H319

[ Precautionary Statements ]:
P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves;type P2 (EN 143) respirator cartridges

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Novel small-molecule SIRT1 inhibitors induce cell death in adult T-cell leukaemia cells.

Sci. Rep. 5 , 11345, (2015)

Adult T-cell leukaemia/lymphoma (ATL) is an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukaemia virus (HTLV)-1. The identification of new molecular targets...

Targeted therapy for the loss of von Hippel-Lindau in renal cell carcinoma: a novel molecule that induces autophagic cell death.

Autophagy 4(7) , 944-6, (2008)

Radiation and conventional cytotoxic chemotherapies are ineffective in treating renal cancer. Approximately 75 percent of renal cell carcinoma (RCC) is associated with an inactivation of the tumor sup...

A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells.

Autophagy 8 , 677-89, (2012)

Autophagy is a conserved constitutive cellular process, responsible for the degradation of dysfunctional proteins and organelles. Autophagy plays a role in many diseases such as neurodegeneration and ...