N-(3-methylphenyl)-4-(pyridin-4-yl)-1,3-thiazol-2-amine

• ChemBase ID: 72475
• Molecular Formular: C15H13N3S
• Molecular Mass: 267.34882
• Monoisotopic Mass: 267.08301843
• SMILES: n1ccc(cc1)c1csc(n1)Nc1cccc(c1)C
• Canonical SMILES: Cc1cccc(c1)Nc1scc(n1)c1ccncc1
• InChI: InChI=1S/C15H13N3S/c1-11-3-2-4-13(9-11)17-15-18-14(10-19-15)12-5-7-16-8-6-12/h2-10H,1H3,(H,17,18)
• InChIKey: KATNUHQNJGNLPW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(3-methylphenyl)-4-(pyridin-4-yl)-1,3-thiazol-2-amine
• IUPAC Traditional name: N-(3-methylphenyl)-4-(pyridin-4-yl)-1,3-thiazol-2-amine
• Synonyms: STF-62247

Database IDs

• CAS Number: 315702-99-9
• PubChem SID: 162037400
• PubChem CID: 704473

CALCULATED PROPERTIES

• Acid pKa: 13.407872
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 4.0743613
• LogD (pH = 7.4): 4.0849023
• Log P: 4.085039
• Molar Refractivity: 76.8744 cm^3
• Polarizability: 30.665493 Å^3
• Polar Surface Area: 37.81 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1041

Research Area

• Description: Cancer

Biological Activity

• Description: STF-62247 is selectively toxic and growth inhibitory to renal cells lacking VHL
• In Vitro: 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. ^[1] 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 . ^[2] 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. ^[3]
• In Vivo: In vivo mouse model, STF-62247 at a dose of 8 mg/kg byby intraperitoneal injection significantly reduces tumor growth of VHL-deficient SN12C tumor cells. ^[1]

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: SN12C and RCC4
• Concentrations: 0 to 40 μM
• Incubation Time: 24 hours
• Methods: 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.
• Protocol: Animal Study ^[1]
• Animal Models: SN12C, SN12C-VHL shRNA or 786-O cells are injected subcutaneously into the flanks of immune-deficient mice.
• Formulation: STF-62247 is dissolved in DMSO and then diluted in water
• Doses: ≤8 mg/kg
• Administration: Administered via i.p.

References

• References: [1] Turcotte S, et al. Cancer Cell. 2008, 14(1), 90-102.
• References: [2] Chan DA, et al. Cell Cycle. 2008, 7(19), 2987-2990.
• References: [3] Anbalagan S, et al. Radiother Oncol. 2012, 103(3), 388-393.

REFERENCES

• Turcotte S, et al. Cancer Cell. 2008, 14(1), 90-102.
• Chan DA, et al. Cell Cycle. 2008, 7(19), 2987-2990.
• Anbalagan S, et al. Radiother Oncol. 2012, 103(3), 388-393.