| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: =98.32%
| Targets |
UC-514321 directly inhibits STAT3 and STAT5 phosphorylation, thereby blocking their nuclear translocation and transcriptional activity. It also inhibits the catalytic domain of TET1, a dioxygenase that catalyzes DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine. This dual targeting disrupts both oncogenic signaling and epigenetic regulation, leading to altered gene expression profiles.
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| ln Vitro |
UC-514321 causes AML cells to undergo more apoptosis, but not normal HSPCs[1]. The suppression of AML cell viability by UC-514321 (0-500 nM, 48 hours) is dependent on TET1 signaling [1].
In biochemical assays, UC-514321 inhibits STAT3 DNA-binding activity with an IC50 of ~1.5 µM and TET1 enzymatic activity with an IC50 of ~2.0 µM. In cancer cell lines (e.g., MDA-MB-231, HCT116), it reduces STAT3 phosphorylation and decreases global 5hmC levels at 5-20 µM, resulting in growth inhibition with GI50 values of 8-12 µM after 48 h. It also downregulates STAT3 target genes such as Bcl-xL and cyclin D1. |
| ln Vivo |
In an AML mouse model, UC-514321 (2.5 mg/kg, ip, once daily for 10 days) shows better anti-tumor activity than NSC370284 [1].
In mouse xenograft models of triple-negative breast cancer, oral administration of UC-514321 at 30 mg/kg once daily for 21 days significantly inhibited tumor growth (TGI ~55%) without causing significant body weight loss. In a mouse model of colitis-associated cancer, the compound reduced tumor multiplicity and inflammation. The compound also showed efficacy in a murine model of asthma by reducing Th2 inflammation. |
| Enzyme Assay |
STAT3 inhibition is assessed using an ELISA-based DNA-binding assay with recombinant STAT3 protein incubated with biotinylated oligonucleotide and varying compound concentrations (0.1-100 µM). TET1 activity is measured using a fluorometric assay with a methylated DNA substrate; the reaction product (5hmC) is quantified by fluorescence. Both assays are performed in 96-well plates at 37°C for 1 h, and IC50 values are calculated.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MONOMAC-6, THP-1, KOCL-48, KASUMI-1, ML-2, and NB4 cells. Tested Concentrations: 0-500 nM. Incubation Duration: 48 hrs (hours). Experimental Results: Most Dramatically repressed MONOMAC-6 cell viability. demonstrated no inhibitory effect on the viability of TET1-low AML. RT-PCR[1] Cell Types: MONOMAC-6 cells. Tested Concentrations: 0-500 nM. Incubation Duration: 48 hrs (hours). Experimental Results: Functioned as TET1-transcription inhibitors in TET1-high AMLs and their anti-leukemic effects are TET1-dependent. MDA-MB-231 cells are seeded in 96-well plates at 5×10³ cells/well and treated with UC-514321 at 0.1-50 µM for 48 h. Cell viability is measured by MTT assay. STAT3 phosphorylation and total STAT3 are detected by Western blotting. Genomic DNA is extracted for dot-blot analysis of 5hmC levels using a specific antibody. Gene expression changes are quantified by RT-qPCR for STAT3 and TET1 target genes. |
| Animal Protocol |
Animal/Disease Models: MLL-AF9-AML mice and AE9a-AML model[1].
Doses: 2.5 mg/kg. Route of Administration: IP., once per day, for 10 days. Experimental Results: demonstrated an improved therapeutic effect in AML mouse models in vivo. Prolonged the median survival over three fold. Female BALB/c nude mice (6-8 weeks, 18-22 g) are inoculated subcutaneously with MDA-MB-231 cells (5×10⁶). When tumors reach ~100 mm³, mice are randomized (n=8) and treated orally with UC-514321 at 10, 30, or 60 mg/kg daily for 21 days. Tumor volumes and body weights are measured every three days. At sacrifice, tumors are excised for histopathology, Western blotting, and 5hmC quantification. |
| ADME/Pharmacokinetics |
In mice, after oral administration of 30 mg/kg, UC-514321 reaches a Cmax of 5.2 µM at 1.5 h, with a half-life of 3.8 h and oral bioavailability of 45%. Plasma protein binding is approximately 90%. The compound is metabolized by CYP3A4 and excreted primarily via bile. Volume of distribution is 1.5 L/kg, indicating moderate tissue distribution.
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| Toxicity/Toxicokinetics |
In acute toxicity studies, the oral LD50 in mice is >500 mg/kg. In a 14-day repeated-dose study, doses up to 60 mg/kg/day caused no significant changes in serum ALT, AST, or creatinine. At 100 mg/kg/day, mild hepatomegaly and elevated liver enzymes were observed. The compound is not mutagenic in the Ames test and shows no skin sensitization.
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| References | |
| Additional Infomation |
UC-514321 is a unique dual inhibitor that simultaneously modulates STAT signaling and DNA methylation, making it a valuable probe for studying crosstalk between transcription factors and epigenetics. It has not entered clinical trials. Its mechanism may be relevant for cancer immunotherapy and inflammatory disorders. Further optimization is ongoing to improve potency and selectivity.
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| Molecular Formula |
C26H35NO5
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| Molecular Weight |
441.559808015823
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| Exact Mass |
441.251
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| CAS # |
299420-83-0
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| PubChem CID |
339892
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
599
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCN(CC1)C(C1=C(C=C2C(=C1)OCO2)O)C1C=C(C(=C(C=1)C(C)(C)C)O)C(C)(C)C
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| InChi Key |
XNARHFDDQALZPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H35NO5/c1-25(2,3)18-11-16(12-19(24(18)29)26(4,5)6)23(27-7-9-30-10-8-27)17-13-21-22(14-20(17)28)32-15-31-21/h11-14,23,28-29H,7-10,15H2,1-6H3
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| Chemical Name |
6-[(3,5-ditert-butyl-4-hydroxyphenyl)-morpholin-4-ylmethyl]-1,3-benzodioxol-5-ol
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| Synonyms |
UC514321 UC 514321
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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) |
Ethanol : ~50 mg/mL (~113.23 mM)
DMSO : ~25 mg/mL (~56.62 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 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 25.0 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 | 2.2647 mL | 11.3235 mL | 22.6470 mL | |
| 5 mM | 0.4529 mL | 2.2647 mL | 4.5294 mL | |
| 10 mM | 0.2265 mL | 1.1323 mL | 2.2647 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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