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| Targets |
SSTC3 targets casein kinase 1α (CK1α), a serine/threonine kinase that plays a critical role in the regulation of the WNT signaling pathway. By activating CK1α, SSTC3 promotes the phosphorylation and degradation of β-catenin, thereby inhibiting WNT signaling. WNT signaling is often dysregulated in cancer, making CK1α a potential target for anticancer therapy. SSTC3 also inhibits HIF1α with a Kd of 32 nM.
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| ln Vitro |
Targeted reduction of HCT116 cell viability occurs with SSTC3 (0-1μM, 5 days). When the mutant CTNNB1 allele that causes its carcinogenic characteristics is removed, this ability is greatly diminished [1].
SSTC3 exhibits potent in vitro activity as a CK1α activator and WNT signaling inhibitor. It has a Kd of 32 nM for CK1α and an EC50 of 30 nM for inhibiting WNT-driven reporter gene activity. It inhibits WNT signaling and has potential antitumor activity. It attenuates the growth of patient-derived metastatic CRC xenografts. These in vitro activities confirm its potential as an anticancer agent. |
| ln Vivo |
A 24-hour course of SSTC3 therapy is possible [1]. In CD-1 mice, the intraperitoneal injection of SSTC3 (25 mg/kg, once daily for 8–12 days) suppresses the progression of colorectal cancer [1]. For a month, SSTC3 (10 mg/kg, intraperitoneally injected once daily) suppresses the growth of tumors caused by Apc mutations [1].
In vivo, SSTC3 attenuates the growth of patient-derived metastatic colorectal cancer (CRC) xenografts, with minimal gastrointestinal toxicity compared to other classes of WNT inhibitors. It has better pharmacokinetic properties than pyvinium. Its ability to inhibit WNT signaling and tumor growth makes it a promising candidate for cancer therapy, particularly for WNT-driven cancers. |
| Enzyme Assay |
In vitro kinase assays for SSTC3 involve measuring its activation of CK1α kinase activity. These assays use recombinant CK1α and a peptide substrate. The enzyme is incubated with the substrate and ATP in the presence of varying concentrations of SSTC3. The phosphorylation of the substrate is measured to determine the EC50. WNT signaling inhibition is assessed using reporter gene assays (e.g., TOPFlash) in cells treated with the compound.
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| Cell Assay |
Cell viability assay[1]
Cell Types: Colorectal cancer (CRC) cell line. Tested Concentrations: 0-1μM. Incubation Duration: 5 days. Experimental Results: diminished vitality. Western Blot Analysis[1] Cell Types: SW403 cells. Tested Concentrations: 100 nM. Incubation Duration: 15 minutes. Experimental Results: Increased beta-catenin phosphate levels. In vitro cellular assays for SSTC3 are conducted in cancer cell lines with dysregulated WNT signaling. Cells are treated with the compound at various concentrations, and WNT signaling activity is measured using reporter gene assays or by assessing the expression of WNT target genes (e.g., AXIN2, MYC) by qPCR. Cell proliferation is measured using MTT or CellTiter-Glo assays. These assays characterize the compound's activity as a WNT signaling inhibitor. |
| Animal Protocol |
Animal/Disease Models: Fiveweeks old Apcmin mice [1].
Doses: 10 mg/kg. Route of Administration: IP 1 month. Experimental Results: Inhibition of Apc mutation-driven tumor growth. Animal/Disease Models: CD-1 mice. Doses: 25 mg/kg. Management: One IP per day for 8-12 days. Experimental Results: Inhibition of growth of HCT116 xenografts. attenuated the growth of this metastatic CRC PDX and Dramatically diminished the cell density of residual cancer. The expression of WNT biomarkers in this CRC PDX was diminished. In vivo animal experiments with SSTC3 are conducted in mouse xenograft models of colorectal cancer (CRC). Tumor-bearing mice are administered SSTC3 at various doses. Tumor growth is monitored, and tumor tissues are harvested for analysis of WNT signaling activity and CK1α activation. Pharmacodynamic studies are performed to confirm target engagement and inhibition of WNT signaling. Gastrointestinal toxicity is assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for SSTC3 indicate that it has better pharmacokinetic properties than pyvinium. It has a molecular weight of approximately 320 g/mol. The compound is soluble in DMSO and is typically stored at -20°C. Its half-life and bioavailability have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
SSTC3 has been evaluated for safety in preclinical studies. It exhibits minimal gastrointestinal toxicity compared to other classes of WNT inhibitors. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. Further toxicity studies would be required to support any potential clinical development.
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| References | |
| Additional Infomation |
4-(N-methyl-N-(4-(trifluoromethyl)phenyl)sulfamoyl)-N-(4-(pyridin-2-yl)thiazol-2-yl)benzamide is a secondary amide formed by the condensation of the carboxyl group of 4-{methyl[4-(trifluoromethyl)phenyl]sulfonyl}benzoic acid with the amino group of 4-(pyridin-2-yl)-1,3-thiazol-2-amine. It is a casein kinase 1α activator (Kd = 32 nM) and inhibits the WNT signaling pathway (EC50 = 30 nM). It possesses antitumor activity and is also an inhibitor of the Wnt signaling pathway. SSTC3 belongs to the class of secondary amides, benzamides, pyridines, sulfonamides, 1,3-thiazolides, and (trifluoromethyl)benzene compounds.
SSTC3 is a novel small-molecule casein kinase 1α (CK1α) activator that inhibits WNT signaling. It has a Kd of 32 nM for CK1α and an EC50 of 30 nM in a WNT-driven reporter gene assay. It has potential antitumor activity and attenuates the growth of patient-derived metastatic CRC xenografts. It exhibits minimal gastrointestinal toxicity compared to other WNT inhibitors. |
| Molecular Formula |
C23H17F3N4O3S2
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| Molecular Weight |
518.5313
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| Exact Mass |
518.069
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| CAS # |
1242422-09-8
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| PubChem CID |
46912682
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
823
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C([H])=C([H])C(C(N([H])C2=NC(=C([H])S2)C2=C([H])C([H])=C([H])C([H])=N2)=O)=C([H])C=1[H])(N(C([H])([H])[H])C1C([H])=C([H])C(C(F)(F)F)=C([H])C=1[H])(=O)=O
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| InChi Key |
HSFAATUFWDDUGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H17F3N4O3S2/c1-30(17-9-7-16(8-10-17)23(24,25)26)35(32,33)18-11-5-15(6-12-18)21(31)29-22-28-20(14-34-22)19-4-2-3-13-27-19/h2-14H,1H3,(H,28,29,31)
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| Chemical Name |
4-[methyl-[4-(trifluoromethyl)phenyl]sulfamoyl]-N-(4-pyridin-2-yl-1,3-thiazol-2-yl)benzamide
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| Synonyms |
SSTC-3; SSTC 3
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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 |
| 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) |
DMSO : ~125 mg/mL (~241.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.01 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 20.8 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: ≥ 2.08 mg/mL (4.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9285 mL | 9.6426 mL | 19.2853 mL | |
| 5 mM | 0.3857 mL | 1.9285 mL | 3.8571 mL | |
| 10 mM | 0.1929 mL | 0.9643 mL | 1.9285 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.
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