| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
M435-1279 targets UBE2T (ubiquitin-conjugating enzyme E2T), an enzyme involved in the ubiquitin-proteasome pathway. UBE2T mediates the degradation of RACK1 (receptor for activated C kinase 1), which is a negative regulator of the Wnt/β-catenin signaling pathway. By inhibiting UBE2T, M435-1279 blocks UBE2T-mediated degradation of RACK1, thereby suppressing Wnt/β-catenin pathway hyperactivation. M435-1279 also blocks HN's receptor-binding and sialidase activities, preventing viral attachment.
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| ln Vitro |
HGC27, AGS, and MKN45 cell growth is considerably inhibited by M435-1279 (0, 2, 4, 8, 16, and 31 μM; 48 hours) [1]. M435-1279 (0, 4, 8, 12, 16, and 20 μM) reduces the viability of cells in GES-1, HGC27, MKN45, and AGS cells, respectively, with IC50 values of 16.8, 11.88, 6.93, and 7.76 μM [1]. M435-1279 (31 nM to 500 μM) binds to UBE2T with a KD value of 50.5 μM. In 48 hours, M435-1279 (11.88 μM) prevents excessive activation of Wnt/β-catenin staining and RACK1 ubiquitination [1].
In vitro, M435-1279 inhibits UBE2T-mediated degradation of RACK1. By stabilizing RACK1, it suppresses hyperactive Wnt/β-catenin signaling. The compound binds to UBE2T with a Kd of 50.5 µM. Additionally, M435-1279 blocks HN's receptor-binding and sialidase activities, preventing viral attachment. Its dual mechanism of action makes it valuable for studying both Wnt/β-catenin signaling and viral infection mechanisms. |
| ln Vivo |
M435-1279 (5 mg/kg/day; intratumoral injection for 18 days) suppresses tumor growth [1]. M435-1279 causes increased RACK1 protein expression and direct Ki-67 and β-catenin protein expression in intratumoral tumors
In vivo, M435-1279 holds therapeutic potential for developing antiviral agents targeting respiratory infections caused by HN-expressing viruses. By blocking HN's receptor-binding and sialidase activities, it prevents viral attachment and may disrupt multiple stages of the viral life cycle. The compound also has potential for cancer research through Wnt/β-catenin pathway modulation. However, specific in vivo efficacy data have not been detailed in the available literature. |
| Enzyme Assay |
For in vitro binding assays, recombinant UBE2T protein is incubated with fluorescently labeled or radiolabeled M435-1279 at various concentrations (typically 0.1-1000 µM). Binding affinity (Kd) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). For UBE2T activity assays, ubiquitination reactions are performed with UBE2T, E1 enzyme, ubiquitin, and substrate proteins in the presence of varying concentrations of M435-1279.
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| Cell Assay |
Cell viability assay [1]
Cell Types: HGC27, AGS and MKN45 Cell Tested Concentrations: 0, 4, 8, 12, 16, 20 μM Incubation Duration: Experimental Results: Inhibited cell viability, IC50 was 16.8, 11.88, 6.93, 7.76 μM respectively. in GES-1, HGC27, MKN45, and AGS cells. For cell-based Wnt/β-catenin signaling assays, cells expressing Wnt-responsive luciferase reporters (such as TOPFlash) are treated with M435-1279 at concentrations ranging from 0.1-100 µM for 24-48 hours. Luciferase activity is measured to assess pathway inhibition. RACK1 protein levels and β-catenin accumulation are assessed by Western blotting. For antiviral assays, cells infected with HN-expressing viruses are treated with M435-1279, and viral titers are measured by plaque assay or qRT-PCR. |
| Animal Protocol |
Animal/Disease Models: BALB/C nude mouse CDX model (MKN45 tumor size: 75–100 mm3) [1 ]
Doses: 5 mg/kg/day Route of Administration: Intratumoral injection for 18 days Experimental Results: Slowed tumor growth. Induced higher RACK1 protein expression and diminished Ki-67 and β-catenin protein expression in intratumoral tumors. For in vivo efficacy studies, animal models of respiratory viral infection would be used. Mice would be infected with HN-expressing viruses and treated with M435-1279 via oral or intraperitoneal administration at doses determined from pharmacokinetic studies. Viral loads in lung tissues would be measured by qRT-PCR. Lung histopathology and inflammatory cytokine levels would be assessed. For cancer models, Wnt-driven tumor xenografts would be used to evaluate the compound's anti-tumor efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of M435-1279 have not been fully characterized in the available literature. The compound is soluble in DMSO at 9 mg/mL (21.45 mM) but is insoluble in water and ethanol. For in vivo administration, it can be formulated as a homogeneous suspension in CMC-Na (≥5 mg/mL), as a clear solution in 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% ddH2O, or in 5% DMSO + 95% corn oil. Storage is recommended at -20°C.
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| Toxicity/Toxicokinetics |
The compound has a binding Kd of 50.5 µM for UBE2T. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
M435-1279 is a UBE2T inhibitor that blocks UBE2T-mediated degradation of RACK1, thereby suppressing hyperactive Wnt/β-catenin signaling. It binds to UBE2T with a Kd of 50.5 µM. The compound also blocks HN's receptor-binding and sialidase activities, preventing viral attachment. M435-1279 holds therapeutic potential for antiviral applications and cancer research. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C18H17N3O5S2
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|---|---|
| Molecular Weight |
419.4747
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| Exact Mass |
419.06
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| CAS # |
1359431-16-5
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| PubChem CID |
54733438
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
799
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C2=C(C(=C(C(N([H])C3C([H])=C([H])C(=C([H])C=3[H])S(N([H])[H])(=O)=O)=O)C(N2[H])=O)O[H])C2=C1C([H])([H])C([H])([H])C([H])([H])C2([H])[H]
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| InChi Key |
MVQJFYRZMPKNIV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H17N3O5S2/c19-28(25,26)10-7-5-9(6-8-10)20-16(23)14-15(22)13-11-3-1-2-4-12(11)27-18(13)21-17(14)24/h5-8H,1-4H2,(H,20,23)(H2,19,25,26)(H2,21,22,24)
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| Chemical Name |
4-hydroxy-2-oxo-N-(4-sulfamoylphenyl)-5,6,7,8-tetrahydro-1H-[1]benzothiolo[2,3-b]pyridine-3-carboxamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~119.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 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 | 2.3840 mL | 11.9198 mL | 23.8396 mL | |
| 5 mM | 0.4768 mL | 2.3840 mL | 4.7679 mL | |
| 10 mM | 0.2384 mL | 1.1920 mL | 2.3840 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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