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| Targets |
IPR-803 targets the urokinase receptor (uPAR), a GPI-anchored protein that plays a key role in cell-surface plasminogen activation and extracellular matrix degradation. It acts as a competitive inhibitor of the protein-protein interaction between uPAR and its ligand, urokinase-type plasminogen activator (uPA). The compound binds directly to uPAR with a Ki of 0.2 uM. By disrupting this interaction, IPR-803 blocks the uPAR/uPA signaling pathway, which is involved in tumor invasion, metastasis, and angiogenesis.
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| ln Vitro |
Delamination of the metal matrix (MMP) and extracellular matrix (ECM) is strongly inhibited by the tumor cell line IPR-803 MDA-MB-231 [1]. IPR-803 promotes apoptosis at a concentration that is concerning for damage, with an IC50 of roughly 30 μM, and destroys MDA-MB-231 cytochromes [1]. MDA-MB-231 cells are stimulated to grow by IPR-803 at an IC50 of 58 μM[1]. IPR-803 (1-50 μM; 24 hours) (0-200 μM; 3 days) boils MDA-MB-231 cells for the least amount of time, with the compound's cytotoxicity causing the least amount of cell inhibition [1]. It has been demonstrated that IPR-803 (50 μM; 30 minutes) inhibits MAPK phosphorylation [1].
In vitro studies have demonstrated that IPR-803 is an effective inhibitor of the uPAR·uPA protein-protein interaction. It binds directly to uPAR with a Ki of 0.2 uM. IPR-803 blocks the invasion of breast cancer cell line MDA-MB-231 and inhibits matrix metalloproteinase (MMP) breakdown of the extracellular matrix (ECM). It also impairs MDA-MB-231 cell adhesion and migration. The compound displays anti-tumor activity in various cancer cell models. Its potency and mechanism have been characterized in multiple biochemical and cellular assays. |
| ln Vivo |
For five weeks, IPR-803 (200 mg/kg; ig; three times a week) can increase body weight, however there isn't a statistically significant difference between the treated and untreated groups [1]. With a gradient of 4% and poor sidewall bioavailability, IPR-803 remains highly concentrated in tumor tissue even after 10 hours [1]. The half-life (t1/2) of IPR-803 is 5[1].
In vivo, IPR-803 has shown anti-tumor activity in preclinical models. As an inhibitor of the uPAR·uPA interaction, it blocks tumor cell invasion and metastasis, which are critical steps in cancer progression. The compound has been investigated in research exploring oxidative stress-related diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. Its in vivo efficacy is attributed to the inhibition of uPAR-mediated signaling and the subsequent reduction in tumor cell migration and extracellular matrix degradation. Further studies are needed to fully characterize its in vivo pharmacokinetics and therapeutic potential. |
| Enzyme Assay |
The in vitro binding assay for IPR-803 involves measuring the inhibition of the uPAR·uPA protein-protein interaction. Surface plasmon resonance (SPR) or fluorescence polarization (FP) assays are typically used. Purified uPAR protein is immobilized on a sensor chip or labeled with a fluorescent probe. Varying concentrations of IPR-803 are incubated with uPAR and a labeled uPA ligand. The displacement of the ligand or the reduction in binding signal is measured. The Ki value of 0.2 uM is determined from competition curves. Data are analyzed using nonlinear regression models.
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| Cell Assay |
Cell proliferation experiment[1]
Cell Types: MDA-MB-231 Cell Tested Concentrations: 0 μM, 50 μM, 150 μM, 200 μM Incubation Duration: 3 days Experimental Results: Shows 90% invasion blocking rate observed at 50 μM . In vitro cellular assays for IPR-803 are conducted using cancer cell lines such as MDA-MB-231 breast cancer cells. Cells are treated with varying concentrations of IPR-803. Cell invasion is assessed using Boyden chamber or Matrigel invasion assays. Cell adhesion is evaluated by measuring the attachment of cells to ECM-coated surfaces. Cell migration is measured using wound-healing or transwell migration assays. Matrix metalloproteinase (MMP) activity is assessed by zymography or ELISA. The compound's effects on these parameters are quantified and compared to untreated controls. All experiments are performed in triplicate. |
| Animal Protocol |
Animal/Disease Models: MDA NSG mouse-MB-231 cell xenograft [1]
Doses: 200 mg/kg Route of Administration: po (oral gavage); three times a week; continued for 5 weeks Experimental Results: Impaired lung metastasis. Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse[1] Doses: 200 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: Oral Experimental Results: t1/2=5 hrs (hrs (hours)). In vivo animal studies for IPR-803 are typically performed in mouse xenograft models of human cancer. Immunocompromised mice are implanted with tumor cells (e.g., MDA-MB-231 breast cancer cells) subcutaneously or orthotopically. When tumors reach a certain size, animals are treated with IPR-803 via intraperitoneal or oral administration. Tumor growth is monitored by caliper measurements. At endpoint, tumors are collected for histopathological analysis, and metastasis to distant organs is assessed. Standard study designs with vehicle control and positive control groups are employed, with 6-10 animals per group. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for IPR-803 are not extensively reported in the available literature. The compound has a molecular weight of 453.49 g/mol and a molecular formula of C23H27N5O5. It is soluble in DMSO at 7.69 mg/mL. For in vivo studies, the compound is typically formulated in suitable vehicles. Storage recommendations: powder at -20degC for 3 years or 4degC for 2 years; in solvent at -80degC for 6 months or -20degC for 1 month. Specific pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution are not provided in the available sources.
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| Toxicity/Toxicokinetics |
Toxicology data for IPR-803 are not extensively reported in the available literature. As an inhibitor of the uPAR·uPA interaction, the compound's safety profile would be related to its effects on the plasminogen activation system, which is involved in various physiological processes including wound healing and tissue remodeling. Preclinical toxicology studies would be required to assess the compound's safety for therapeutic development. No specific toxicity data, including LD50 values or organ toxicity profiles, are available in the public domain. The compound is for research use only.
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| References | |
| Additional Infomation |
IPR-803 is a potent inhibitor of the uPAR·uPA protein-protein interaction with a Ki of 0.2 uM. It binds directly to uPAR and blocks the interaction with its ligand uPA. The compound displays anti-tumor activity by inhibiting cancer cell invasion, adhesion, and migration. IPR-803 has been investigated in research exploring oxidative stress-related diseases. It is a valuable research tool for studying the uPAR/uPA signaling pathway and cancer metastasis. The compound is for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C27H23N3O4
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| Molecular Weight |
453.489226579666
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| Exact Mass |
453.168
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| CAS # |
892243-35-5
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| PubChem CID |
3675673
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
769
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=C(NC2=C3C4=C(C5C(C3=O)=CC=CC=5)ON=C4C(N3CCCCCC3)=C2)C=CC=1)O
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| InChi Key |
UAEULQWANHYLGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H23N3O4/c31-25-18-10-3-4-11-19(18)26-23-22(25)20(28-17-9-7-8-16(14-17)27(32)33)15-21(24(23)29-34-26)30-12-5-1-2-6-13-30/h3-4,7-11,14-15,28H,1-2,5-6,12-13H2,(H,32,33)
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| Chemical Name |
3-[[12-(azepan-1-yl)-8-oxo-15-oxa-14-azatetracyclo[7.6.1.02,7.013,16]hexadeca-1(16),2,4,6,9,11,13-heptaen-10-yl]amino]benzoic acid
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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 : ~7.69 mg/mL (~16.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.77 mg/mL (1.70 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 7.7 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 | 2.2051 mL | 11.0256 mL | 22.0512 mL | |
| 5 mM | 0.4410 mL | 2.2051 mL | 4.4102 mL | |
| 10 mM | 0.2205 mL | 1.1026 mL | 2.2051 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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