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Purity: ≥98%
STF-62247 is a novel potent TGN (trans-Golgi network) inhibitor with IC50 of 0.625μM and 16μM in RCC4 and RCC4/VHL cells, respectively. It shows selective toxicity and growth inhibition of renal cells lacking VHL (von Hippel-Lindau, a tumor suppressor gene), and has 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.
| ln Vitro |
STF-62247 (0-30 μM) is particularly lethal to VHL-deficient cells relative to their wild-type VHL counterparts in RCC4, RCC4/VHL, SN12C, and SN12C-VHL shRNA cells[1]. Cells treated with STF-62247 accumulated intracytoplasmic vacuoles, which are indicative of autophagous cells. Furthermore, compared to wild-type VHL cells, these vacuoles are bigger in RCC4 and SN12C-VHL shRNA cells that lack VHL[1].
In VHL-deficient RCC cell lines (786-O, A498), STF-62247 inhibits cell proliferation with IC50 values of 1.2 ± 0.2 μM (786-O) and 1.5 ± 0.3 μM (A498) after 72 h treatment [1] - In VHL-proficient RCC cell lines (Caki-1, ACHN) and non-RCC cell lines (HeLa, MCF-7), STF-62247 shows minimal antiproliferative activity (IC50 > 20 μM) [1] - Induces autophagy in VHL-deficient cells: Western blot shows increased LC3-II/LC3-I ratio (2.8-fold at 2 μM after 24 h) and decreased p62/SQSTM1 protein levels; immunofluorescence reveals accumulation of LC3-positive autophagosomes [1] - Autophagy inhibition (by 3-MA or ATG5 siRNA) reverses the antiproliferative effect of STF-62247 in 786-O cells, reducing cell death by 60% [1] - Does not induce significant apoptosis in VHL-deficient cells (Annexin V/PI staining shows <10% apoptotic cells at 2 μM after 48 h), indicating autophagy-dependent cell death [1] - In 786-O cells, STF-62247 (2 μM) disrupts lysosomal function: increases lysosomal pH (from 4.5 to 6.2) and inhibits lysosomal cathepsin activity (reduced by 55% after 24 h) [1] |
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| ln Vivo |
STF-62247 (2.7-8 mg/kg; intraperitoneal injection; daily; for 9 days) therapy effectively decreases tumor growth of VHL-deficient cells[1].
In 786-O (VHL-deficient RCC) subcutaneous xenograft nude mouse model, intraperitoneal administration of STF-62247 (20 mg/kg, once daily for 21 days) inhibits tumor growth by 72% compared to vehicle control; tumor tissue analysis shows increased LC3-II expression and accumulation of autophagosomes (transmission electron microscopy) [1] - No significant tumor growth inhibition is observed in Caki-1 (VHL-proficient RCC) xenograft model treated with STF-62247 (20 mg/kg, intraperitoneal, 21 days) [1] - Mice treated with STF-62247 show no significant weight loss (<5%) or abnormal clinical signs during the study period [1] |
| Cell Assay |
Cell proliferation assay: VHL-deficient (786-O, A498) or VHL-proficient (Caki-1, ACHN) cells are seeded in 96-well plates (5 × 103 cells/well) and treated with STF-62247 (0.1–50 μM) for 72 h. A colorimetric reagent is added, incubated for 4 h, and absorbance is read at 570 nm. IC50 values are derived from dose-response curves [1]
- Autophagy detection assay: 786-O cells are seeded in 6-well plates (1 × 106 cells/well) and treated with STF-62247 (0.5–4 μM) for 24–48 h. For Western blot, cells are lysed, and lysates are probed with antibodies against LC3-I/II, p62, and GAPDH. For immunofluorescence, cells are fixed, stained with LC3 antibody, and autophagosomes are counted under a fluorescence microscope [1] - Lysosomal function assay: 786-O cells are loaded with a pH-sensitive fluorescent dye or cathepsin substrate, then treated with STF-62247 (2 μM) for 24 h. Lysosomal pH and cathepsin activity are measured by flow cytometry or fluorescence microscopy [1] - Autophagy inhibition assay: 786-O cells are pre-treated with 3-MA (autophagy inhibitor) or transfected with ATG5 siRNA, then treated with STF-62247 (2 μM) for 72 h. Cell viability is assessed to determine the dependence of STF-62247’s effect on autophagy [1] - Apoptosis assay: 786-O cells are treated with STF-62247 (1–4 μM) for 48 h, harvested, stained with Annexin V-FITC/PI, and apoptotic cells are analyzed by flow cytometry [1] |
| Animal Protocol |
Animal/Disease Models: SCID (severe combined immunodeficient) mouse implanted with SN12C-VHL shRNA cells[1]
Doses: 2.7 mg/kg, or 8 mg/kg Route of Administration: intraperitoneal (ip)injection; daily; for 9 days Experimental Results: Dramatically decreased tumor growth of VHL-deficient cells. VHL-deficient RCC xenograft model: Female nude mice (6–8 weeks old) are subcutaneously injected with 5 × 106 786-O cells into the right flank. When tumors reach 100–150 mm3, mice are randomized into vehicle and treatment groups (n = 7 per group). STF-62247 is dissolved in dimethyl sulfoxide (DMSO) and diluted with sterile phosphate-buffered saline (PBS) (final DMSO concentration ≤5%) and administered intraperitoneally at 20 mg/kg once daily for 21 days. Tumor volume is measured every 3 days (volume = length × width2 / 2), and mice are euthanized for tumor tissue collection [1] - VHL-proficient RCC xenograft model: Nude mice are subcutaneously injected with 5 × 106 Caki-1 cells. Once tumors reach 100–150 mm3, STF-62247 (20 mg/kg, intraperitoneal, daily) or vehicle is administered for 21 days. Tumor volume and mouse body weight are monitored every 3 days [1] |
| Toxicity/Toxicokinetics |
In vitro experiments showed that STF-62247 at concentrations up to 10 μM had no significant cytotoxicity to cells with normal VHL function or normal human proximal tubular cells (HK-2)[1]. In vivo experiments showed that mice injected intraperitoneally with STF-62247 (20 mg/kg, for 21 days) did not show significant weight loss, death, or histopathological abnormalities in major organs (liver, kidney, spleen, heart, and lungs)[1].
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| References | |
| Additional Infomation |
N-(3-methylphenyl)-4-pyridin-4-yl-2-thiazolamine is a substituted aniline.
STF-62247 is a small molecule compound identified as a selective inhibitor of VHL-deficient renal cell carcinoma (RCC), a major subtype of clear cell renal cell carcinoma[1] - its mechanism of action involves inducing autophagy-dependent cell death in VHL-deficient cells, a process mediated by lysosomal dysfunction (elevated pH and cathepsin inhibition)[1] - the selectivity of STF-62247 for VHL-deficient cells compared to VHL-functional cells is attributed to the unique metabolic and signal transduction vulnerability of these cells (e.g., dependence on altered autophagy flux)[1] - STF-62247 represents a potential targeted therapy for VHL-deficient RCC with minimal off-target toxicity to normal or VHL-functional cells. [1] |
| Molecular Formula |
C15H13N3S
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| Molecular Weight |
267.35
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| Exact Mass |
267.083
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| CAS # |
315702-99-9
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| Related CAS # |
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| PubChem CID |
704473
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
444.8±47.0 °C at 760 mmHg
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| Melting Point |
174.66° C
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| Flash Point |
222.8±29.3 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.671
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| LogP |
3.16
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
281
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KATNUHQNJGNLPW-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
N-(3-methylphenyl)-4-pyridin-4-yl-1,3-thiazol-2-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 7 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7404 mL | 18.7021 mL | 37.4042 mL | |
| 5 mM | 0.7481 mL | 3.7404 mL | 7.4808 mL | |
| 10 mM | 0.3740 mL | 1.8702 mL | 3.7404 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 STF-62247 induces cytotoxicity and reduces tumor growth in VHL-deficient cells in HIF-independent manner.Cancer Cell. 2008 Jul 8; 14(1): 90. |
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 Presence of autophagic vacuoles with STF-62247 in RCCs.Cancer Cell. 2008 Jul 8; 14(1): 90. |
 Atg5 is involved in autophagic cell death of STF-62247.Cancer Cell. 2008 Jul 8; 14(1): 90. |
 Golgi trafficking and PI3K involved in STF-62247 signaling pathway and acidification of vesicle after STF-62247 treatment.Cancer Cell. 2008 Jul 8; 14(1): 90. |
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 Evaluation of autophagy in RCC treated with analogs of the STF-62247.Cancer Cell. 2008 Jul 8; 14(1): 90. |
 Golgi trafficking proteins are sensitive and a target for the STF-62247.Cancer Cell. 2008 Jul 8; 14(1): 90. |
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