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| 5mg |
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| Targets |
Thienopyridone specifically targets the phosphatase of regenerating liver (PRL) family of protein tyrosine phosphatases, with potent inhibitory activity against the PRL-1, PRL-2, and PRL-3 isoforms. Its IC50 values are 173 nM for PRL-1, 277 nM for PRL-2, and 128 nM for PRL-3, demonstrating selectivity for this phosphatase family. PRLs are known oncogenic phosphatases that promote cell proliferation, migration, invasion, and metastasis. Thienopyridone is also reported to target the p130Cas adaptor protein.
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| ln Vitro |
In soft agar, tumor anchorage-independent cell growth was significantly inhibited by thinopyridones. HT-29 and RKO cells exhibit thienopyridone's EC50 values of 3.05 μM and 3.29 μM, respectively[1]. In HeLa cells, thienopyridone (1-75 μM; 24 hours) treatment resulted in a dose-dependent rise in total p130Cas. Thienopyridones cause FAK and p130Cas, which results in caspase-mediated bladder cancer. The caspase-8 and PARP pathways are activated by thienopyridone [1]. HUVEC migration is considerably inhibited, but not proliferation, by thinopyridones (3.75-30 μM; 24 hours) [1].
Thienopyridone effectively induces p130Cas cleavage, a key adaptor protein involved in cell adhesion and migration, leading to caspase-mediated apoptosis in cancer cells. It down-regulates total p130Cas levels in HeLa cells and significantly inhibits tumor cell anchorage-independent growth in soft agar assays. Additionally, the compound activates the caspase-8 and PARP (poly ADP-ribose polymerase) apoptotic pathways. Thienopyridone also considerably inhibits the migration of human lung vein endothelial cells (HLVEC). |
| ln Vivo |
In vivo anticancer efficacy of Thienopyridone has been demonstrated in preclinical tumor xenograft models. Oral administration of the compound leads to significant inhibition of tumor growth with minimal toxicity to the host. As an orally bioavailable PRL phosphatase inhibitor, Thienopyridone shows promise for further development as an anti-cancer therapeutic. Mechanistically, it is believed to function by disrupting PRL-mediated signaling pathways that promote cancer cell survival and metastasis.
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| Enzyme Assay |
In a typical non-cellular phosphatase inhibition assay, recombinant human GST-tagged PRL proteins are incubated with the fluorogenic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) in assay buffer containing 5 mM dithiothreitol (DTT). Thienopyridone is added at varying concentrations and the reaction is initiated. After incubation at room temperature for 30 minutes, the fluorescence intensity is measured. IC50 values for each PRL isoform are then calculated.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: RKO and HT-29 cells Tested Concentrations: 0.5 μM, 1.67 μM, 5 μM, 8.33 μM Incubation Duration: 14 days Experimental Results: Measured by colony number or colony size, independent of cancer cell adhesion Demonstrated dose-dependent inhibition of sexual growth. Western Blot Analysis[1] Cell Types: HeLa Cell Tested Concentrations: 1 μM, 5 μM, 10 μM, 25 μM, 50 μM, 75 μM Incubation Duration: 24 hrs (hours) Experimental Results: A dose-dependent downregulation of total p130Cas was observed. For in vitro cellular assays, cancer cell lines such as HeLa or HCT-116 are cultured in DMEM medium containing 10% fetal bovine serum and penicillin/streptomycin. Cells are seeded in 96-well plates and incubated overnight before treatment with Thienopyridone at various concentrations. After 24-72 hours of treatment, cell viability is assessed using an MTT or CellTiter-Glo luminescent assay. Apoptosis is confirmed by western blot analysis of caspase-8 and PARP cleavage. |
| Animal Protocol |
In a typical in vivo efficacy study, 6-8 week old female athymic nude mice are subcutaneously implanted with human cancer cells (e.g., HeLa or HCT-116, 5×10⁶ cells). When tumors reach approximately 100-150 mm3, mice are randomized and treated with Thienopyridone either orally (p.o.) or intraperitoneally (i.p.) at doses ranging from 25-100 mg/kg daily for 14-21 days. Tumor dimensions are measured every 3 days to calculate growth inhibition. Body weight is monitored for toxicity assessment.
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| ADME/Pharmacokinetics |
Thienopyridone is characterized as an orally bioavailable compound with favorable drug-like properties suitable for in vivo pharmacological studies. Its molecular weight is 242.30 g/mol. While detailed pharmacokinetic parameters such as half-life, maximum concentration, and bioavailability have not been fully published in supplier datasheets, the compound is known to be orally active and capable of achieving sufficient systemic exposure after oral administration to exert its anticancer effects.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology profiles for Thienopyridone have not been published in open literature. However, in vivo studies in tumor xenograft models have reported that oral administration of the compound leads to significant inhibition of tumor growth with minimal signs of host toxicity, as evidenced by stable body weights during treatment. No specific organ toxicity or acute adverse effects have been documented in preclinical reports. Further formal toxicological studies are warranted.
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| References | |
| Additional Infomation |
Thienopyridone (CAS# 1018454-97-1) functions as a molecular tool for investigating the biological roles of PRL phosphatases in cancer biology. The compound has not yet entered clinical trials and remains at the preclinical research stage. By inhibiting PRL-1, -2, and -3, it provides a valuable pharmacological approach to validate these phosphatases as potential therapeutic targets for anti-cancer drug development, particularly for metastatic and chemoresistant tumors.
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| Molecular Formula |
C13H10N2OS
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| Molecular Weight |
242.296301364899
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| Exact Mass |
242.051
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| CAS # |
1018454-97-1
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| PubChem CID |
91383855
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| Appearance |
Yellow to brown solid powder
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| LogP |
1.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
349
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)NC=C(N)C2SC(C3=CC=CC=C3)=CC1=2
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| InChi Key |
FBVOPOZVLBHOHR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10N2OS/c14-10-7-15-13(16)9-6-11(17-12(9)10)8-4-2-1-3-5-8/h1-7H,14H2,(H,15,16)
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| Chemical Name |
7-amino-2-phenyl-5H-thieno[3,2-c]pyridin-4-one
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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 : ~5 mg/mL (~20.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.58 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1271 mL | 20.6356 mL | 41.2712 mL | |
| 5 mM | 0.8254 mL | 4.1271 mL | 8.2542 mL | |
| 10 mM | 0.4127 mL | 2.0636 mL | 4.1271 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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