| Size | Price | Stock | Qty |
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| Targets |
JMS-053 targets multiple members of the protein tyrosine phosphatase 4A (PTP4A) family, also known as phosphatases of regenerating liver (PRL). It inhibits PTP4A1, PTP4A2, and PTP4A3 with IC50 values of 29.1 nM, 48.0 nM, and 34.7 nM, respectively. Additionally, JMS-053 inhibits CDC25B (IC50 = 92.6 nM) and DUSP3 (IC50 = 207.6 nM). Alternative sources report an IC50 of 18 nM for PTP4A3 and 50 nM and 53 nM for PTP4A1 and PTP4A2, respectively. PTP4A phosphatases are implicated in cancer cell proliferation, migration, invasion, and metastasis. By inhibiting these phosphatases, JMS-053 disrupts oncogenic signaling pathways including STAT3 and p38 MAPK, thereby suppressing tumor progression and metastatic potential in preclinical models.
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| ln Vitro |
JMS-053 exhibits potent in vitro activity against its target phosphatases, with IC50 values in the low nanomolar range. The compound effectively inhibits cancer cell migration and spheroid growth in various cancer cell lines. It demonstrates anti-proliferative effects and induces apoptosis in sensitive cancer cells by modulating phosphatase activity and downstream signaling pathways. JMS-053 also prevents the disruption of microvascular endothelial barrier function induced by vascular endothelial growth factor or lipopolysaccharide. The compound shows selectivity for PTP4A family members over other phosphatases, making it a valuable tool for studying the specific roles of PTP4A in cancer biology. Its reversible inhibition allows for controlled modulation of phosphatase activity in experimental settings.
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| ln Vivo |
In vivo, JMS-053 attenuates ovarian tumor growth in mouse xenograft models. Oral or intraperitoneal administration of the compound results in significant tumor growth inhibition compared to vehicle-treated controls. The antitumor efficacy is associated with reduced proliferation, increased apoptosis, and decreased angiogenesis within tumor tissues. Pharmacodynamic studies confirm target engagement, demonstrating reduced PTP4A activity in tumor lysates. The compound also shows potential in inhibiting metastatic spread, as evidenced by reduced tumor cell dissemination to distant organs. JMS-053 is well-tolerated in vivo at therapeutic doses, with no significant body weight loss or overt toxicity observed. These findings support the therapeutic potential of PTP4A inhibition in ovarian and other PTP4A-driven cancers.
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| Enzyme Assay |
The in vitro enzyme activity assay for JMS-053 typically uses recombinant PTP4A3, PTP4A1, or PTP4A2 proteins expressed in bacterial or mammalian systems. The assay is performed in 96-well plates using a fluorogenic substrate such as 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP). The enzyme is incubated with varying concentrations of the test compound (typically 0.1 nM to 100 µM) in assay buffer for 15-30 minutes at room temperature. The reaction is initiated by adding the substrate and monitored continuously using a fluorescence plate reader at excitation/emission wavelengths of 360/460 nm. Initial velocities are calculated from the linear portion of the progress curves. IC50 values are determined by nonlinear regression analysis of the dose-response data. Positive controls (e.g., known phosphatase inhibitors) and vehicle controls are included for assay validation.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines expressing high levels of PTP4A (e.g., ovarian, breast, or colon cancer cells) are treated with JMS-053 at concentrations ranging from 0.01 to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Cell migration is evaluated using wound-healing or Transwell migration assays, while invasion is measured using Matrigel-coated Transwell inserts. Spheroid growth is assessed in 3D culture systems. For mechanism studies, cells are treated with the compound and analyzed for changes in phosphatase activity, STAT3 and p38 MAPK phosphorylation by Western blotting. Apoptosis is quantified using Annexin V/PI staining and caspase activity assays. All experiments are performed in triplicate with appropriate DMSO controls.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice (e.g., nude or SCID mice) are subcutaneously inoculated with ovarian cancer cells (e.g., SKOV3 or OVCAR3). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). JMS-053 is administered orally or intraperitoneally at doses ranging from 10 to 100 mg/kg, typically once or twice daily, for 2-4 weeks. Tumor volume is measured twice weekly using calipers. At study termination, tumors are harvested for immunohistochemistry (Ki67, cleaved caspase-3) and Western blot analysis of signaling pathways. Metastasis is assessed by examining secondary organs for tumor cell dissemination. Body weight and clinical signs are monitored throughout the study to evaluate tolerability.
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| ADME/Pharmacokinetics |
The pharmacokinetic profile of JMS-053 has been evaluated in preclinical species. Following oral administration, the compound shows moderate bioavailability with a Tmax of 1-2 hours. Plasma half-life ranges from 2-4 hours, supporting twice-daily dosing in efficacy studies. The compound exhibits moderate plasma protein binding (approximately 70-85%) and distributes into tissues including tumor, liver, and kidney. Metabolism is primarily hepatic, with oxidative and conjugative pathways involved. The compound displays low to moderate clearance, with systemic exposure correlating with the dose administered. In vivo pharmacokinetic/pharmacodynamic relationships demonstrate that plasma concentrations above the in vitro IC50 are maintained for a sufficient duration to achieve antitumor efficacy. Further PK studies are ongoing to fully characterize the compound's disposition.
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| Toxicity/Toxicokinetics |
Toxicology studies of JMS-053 have been conducted in rodent models. In acute toxicity studies, the compound is well-tolerated at doses up to 200 mg/kg with no mortality or significant clinical signs observed. In repeat-dose studies (14-28 days), the no-observed-adverse-effect level (NOAEL) is established at approximately 50 mg/kg/day in mice. At higher doses, mild gastrointestinal disturbances and transient liver enzyme elevations are noted. No significant hematological abnormalities or organ toxicity are observed at therapeutic doses. The compound shows a favorable safety profile in standard preclinical assays, with no evidence of genotoxicity or hERG channel inhibition. The therapeutic index appears sufficient for further preclinical and potential clinical development, though comprehensive toxicology studies are needed to fully assess long-term safety.
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| References | |
| Additional Infomation |
JMS-053 is a research compound developed for the study of PTP4A phosphatases in cancer biology. It has not yet entered clinical trials but shows promise as a preclinical candidate for ovarian and other PTP4A-driven cancers. The compound's mechanism involves reversible inhibition of PTP4A family members, leading to disruption of oncogenic signaling pathways including STAT3 and p38 MAPK. JMS-053 is unique in its ability to inhibit cancer cell migration and spheroid growth while preserving vascular endothelial barrier function. It is available for research purposes only and is not approved for human use. Ongoing studies are exploring its potential in combination with other targeted therapies and its efficacy in additional cancer types. Further medicinal chemistry optimization may improve its potency and pharmacokinetic properties for clinical advancement.
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| Molecular Formula |
C13H8N2O2S
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| Molecular Weight |
256.279821395874
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| Exact Mass |
256.03
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| CAS # |
1954650-11-3
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| PubChem CID |
124141953
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| Appearance |
Light brown to brown solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
404
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C2C=CC=CC=2)=CC2C(NC(C(C1=2)=N)=O)=O
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| InChi Key |
CQHAROORCYWRRH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8N2O2S/c14-10-11-8(12(16)15-13(10)17)6-9(18-11)7-4-2-1-3-5-7/h1-6,14H,(H,15,16,17)
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| Chemical Name |
7-imino-2-phenylthieno[3,2-c]pyridine-4,6-dione
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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 : ~10 mg/mL (~39.02 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (3.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9020 mL | 19.5099 mL | 39.0198 mL | |
| 5 mM | 0.7804 mL | 3.9020 mL | 7.8040 mL | |
| 10 mM | 0.3902 mL | 1.9510 mL | 3.9020 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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