| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of T3Inh-1 is ppGalNAc-T3, a glycosyltransferase enzyme involved in the initiation of mucin-type O-glycosylation. This enzyme is implicated in at least two medically important pathways: cancer metastasis and stabilization of FGF23, a hormone that regulates phosphate levels in the bloodstream. By inhibiting ppGalNAc-T3, T3Inh-1 modulates both pathways. The compound is a selective small-molecule inhibitor.
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| ln Vitro |
T3Inh-1 (5 µM; 24-48 hours; 5 µM; MDA-MB231 cells) exhibits remarkable efficacy, exhibiting >80% and 98% inhibition of migration and invasion, respectively, with no appreciable impact on cell proliferation[1]. shows no toxicity and has no effect on the proliferation of HEK cells[1]. The cleavage of FGF23 is increased by T3Inh-1 (HEK cells; 6 hours)[1].
T3Inh-1 inhibits ppGalNAc-T3 enzymatic activity with an IC₅₀ of 7 µM. In MDA-MB231 breast cancer cells, T3Inh-1 (5 µM; 24-48 hours) inhibits migration by >80% and invasion by 98% without affecting cell proliferation. This demonstrates its potent anti-metastatic activity. The compound reduces FGF23 hormone levels in tissue cells. |
| ln Vivo |
T3Inh-1 (25 or 50 mg/kg; ip) increases FGF23 cleavage by blocking ppGalNAc-T3-mediated glycan-masking of FGF23[1].
T3Inh-1 reduces FGF23 hormone levels in mice without causing toxic side effects. This confirms its in vivo target engagement and suggests that ppGalNAc-T3 inhibition can modulate systemic FGF23 levels. The compound increases FGF23 cleavage in vivo at 25-50 mg/kg (i.p.) in mice. It exacerbates ischemic AKI in murine models, mirroring GALNT3 knockdown. |
| Enzyme Assay |
ppGalNAc-T3 enzymatic activity is measured using a radiometric or fluorescence-based glycosyltransferase assay with a peptide acceptor substrate and UDP-GalNAc as the donor. The IC₅₀ of T3Inh-1 (7 µM) is determined by measuring the inhibition of enzymatic activity at varying compound concentrations.
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| Cell Assay |
T3Inh-1 is evaluated in MDA-MB231 breast cancer cells. Cells are treated with 5 µM T3Inh-1 for 24-48 hours. Migration is assessed using wound healing or transwell assays, while invasion is evaluated using Matrigel-coated transwell chambers. Cell proliferation is measured to confirm that the anti-migratory and anti-invasive effects are not due to cytotoxicity.
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| Animal Protocol |
Animal/Disease Models: Wild-type C57BL/6 six to eight week old mice[1]
Doses: 25 or 50 mg/kg Route of Administration: intraperitoneal (ip) injection (Dissolved in DMSO at 25 and 50 mg/ml then further diluted with PEG400 to create 5 and 10 mg/ml stocks for injection) Experimental Results: Caused a robust and statistically significant increase the ratio of cleaved/intact FGF23 at the tested 25 and 50 mg/kg concentrations. In vivo studies are conducted in mice to evaluate T3Inh-1's effects on FGF23 hormone levels. Mice are administered T3Inh-1, and serum FGF23 levels are measured to assess target engagement. Tumor xenograft models may also be used to evaluate the compound's anti-metastatic potential. The compound increases FGF23 cleavage in vivo at 25-50 mg/kg (i.p.) in mice. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for T3Inh-1 have not been reported in the available literature. As a small molecule inhibitor, its absorption, distribution, metabolism, and excretion properties would need to be characterized for further development. The compound is soluble in DMSO at 10 mg/mL (with pH adjustment to 6 with HCl).
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| Toxicity/Toxicokinetics |
T3Inh-1 reduces FGF23 hormone levels in mice without causing any toxic side effects. This favorable safety profile has been demonstrated in preclinical studies. No specific toxicity data beyond this observation have been reported. The compound is for research use only.
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| References |
[1]. Song L, et al. Inhibitor of ppGalNAc-T3-mediated O-glycosylation blocks cancer cell invasiveness and lowers FGF23 levels. Elife. 2017;6:e24051. Published 2017 Mar 31.
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| Additional Infomation |
T3Inh-1 is a research compound not approved for clinical use. It is a valuable tool for studying ppGalNAc-T3 function in O-glycosylation, cancer metastasis, and FGF23 regulation. Its ability to prevent breast cancer cell migration and invasion positions it as a potential lead for anti-metastatic drug development. The compound is a potent and selective inhibitor of ppGalNAc-T3.
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| Molecular Formula |
C27H20N6O3
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|---|---|
| Molecular Weight |
476.49
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| Exact Mass |
476.16
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| CAS # |
50440-30-7
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| PubChem CID |
4532204
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.431g/cm3
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| Boiling Point |
662.7ºC at 760mmHg
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| Flash Point |
354.6ºC
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| Index of Refraction |
1.783
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| LogP |
7.019
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
726
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1C(=O)NC2=CC=C(C=C2)NC3=CC=NC=C3)NC4=C5C=C(C=CC5=NC=C4)[N+](=O)[O-]
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| InChi Key |
KUBNLSZSAIOAMS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H20N6O3/c34-27(32-21-7-5-19(6-8-21)30-22-11-14-28-15-12-22)18-1-3-20(4-2-18)31-26-13-16-29-25-10-9-23(33(35)36)17-24(25)26/h1-17H,(H,28,30)(H,29,31)(H,32,34)
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| Chemical Name |
4-[(6-nitroquinolin-4-yl)amino]-N-[4-(pyridin-4-ylamino)phenyl]benzamide
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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 (20.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.10 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.10 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 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 | 2.0987 mL | 10.4934 mL | 20.9868 mL | |
| 5 mM | 0.4197 mL | 2.0987 mL | 4.1974 mL | |
| 10 mM | 0.2099 mL | 1.0493 mL | 2.0987 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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