| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
GS-143 targets the E3 ubiquitin ligase β-TrCP1 (also known as SCFβTrCP1). It inhibits IκBα ubiquitination with an IC₅₀ of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. By blocking IκBα ubiquitination and subsequent proteasomal degradation, GS-143 prevents the release of NF-κB from its inhibitory complex, thereby suppressing NF-κB activation and target gene transcription. The compound does not inhibit proteasome activity.
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| ln Vitro |
In vitro, Th2 cells are resistant to factor-induced apoptosis when exposed to GS143 (10 μM or 20 μM), but not Th1 cells. In a dose-dependent manner, GS143 strongly suppresses the Th2 pathway's ability to produce IL-4 [1]. TNFα-induced NF-κB regulation is inhibited by GS143, with an average IC50 value of 10.5 μM. With an IC50 value of 6.1 μM, GS143 also suppresses TNFα-induced ICAM-1 expression in HT-29 circulation. LPS-activated THP-1 cells showed inhibited production of TNFα and IL-1β, with IC50 values of 2.1 μM and 5.3 μM, respectively. p53 and β-catenin are not inhibited by GS143[2].
In vitro, GS-143 inhibits IκBα ubiquitination with an IC₅₀ of 5.2 μM. It suppresses NF-κB activation and transcription of target genes. The compound blocks LPS-induced expression of inflammatory cytokines in human myelomonocytic cells. GS-143 also triggers a novel signaling pathway to reactivate latent HIV-1 that leads to unconventional activation of NF-κB p65, by initiating noncanonical signaling via NIK, followed by activation of IKK leading to phosphorylation of p65 on S536 and its nuclear translocation. |
| ln Vivo |
Intranasal scent administered once to BALB/c mice containing 16–32 μg/body of GS143 causes transcription factor receptors to become activated by NF-κB. Additionally, GS143 therapy causes the development of Th2 cytokines and eotaxin in the airways, as well as transcription factor activation of eosinophils and eosinophils into the airways [1].
In vivo, GS-143 has been studied in animal models for its anti-asthma effects. In OVA-sensitized mice, the compound reduces inflammatory cytokine expression. As a β-TrCP1 ligase inhibitor, it has potential applications in inflammatory diseases, HIV latency reversal, and cancer research. The compound's ability to modulate NF-κB signaling without affecting proteasome activity makes it a valuable tool for studying NF-κB pathway regulation. |
| Enzyme Assay |
IκBα ubiquitination assays: Cell lysates or in vitro ubiquitination reaction mixtures containing SCFβTrCP1 E3 ligase complex, phosphorylated IκBα substrate, E1 and E2 enzymes, and ubiquitin are incubated with GS-143 at various concentrations (typically 0.1-50 μM). Ubiquitination of IκBα is detected by Western blot using anti-ubiquitin or anti-IκBα antibodies. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Human myelomonocytic cells (e.g., THP-1) are cultured in RPMI-1640 medium with 10% FBS at 37°C with 5% CO₂. Cells are pre-treated with GS-143 at various concentrations (typically 1-50 μM) and then stimulated with LPS. Inflammatory cytokine levels (TNF-α, IL-1β, IL-6) in supernatant are measured by ELISA. NF-κB activation is assessed by measuring IκBα degradation and p65 nuclear translocation via Western blot and immunofluorescence.
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse (7-8 weeks) injected with ovalbumin [1]
Doses: 16 μg/body or 32 μg/body Route of Administration: intranasal administration; primary Experimental Results:inhibition of lungs of sensitized mice Antigen-induced NF-κB activation. In vivo studies are conducted in rodent models of inflammation or asthma. GS-143 is formulated in suitable vehicles and administered via intraperitoneal, intravenous, or other routes at specified doses. In OVA-sensitized mice, inflammatory cytokine expression is measured in lung tissues. For HIV latency studies, appropriate animal models are used to evaluate LRA activity. |
| ADME/Pharmacokinetics |
GS-143 has molecular formula C₂₈H₁₉FN₂O₄ and molecular weight 466.47. It is soluble in DMSO (10 mM). Purity is >98%. The compound is typically stored as a powder at -20°C and protected from light and moisture. It is a β-TrCP1 ligase inhibitor that inhibits IκBα ubiquitination without affecting proteasome activity.
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| References | |
| Additional Infomation |
GS-143 is a specific small molecule inhibitor of the E3 ubiquitin ligase β-TrCP that selectively inhibits IκBα ubiquitination with an IC₅₀ of 5.2 μM. It suppresses NF-κB activation and transcription of target genes without inhibiting proteasome activity. The compound exhibits potent latency reversing agent activity in primary cell models of HIV-1 latency by triggering a novel signaling pathway that leads to unconventional activation of NF-κB p65. GS-143 also has anti-asthma effects in OVA-sensitized mice. It is intended for research purposes only.
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| Molecular Formula |
C28H19FN2O4
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|---|---|
| Molecular Weight |
466.459870576859
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| Exact Mass |
466.132
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| CAS # |
916232-21-8
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| PubChem CID |
121513876
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| Appearance |
Pink to red solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
844
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CC(N2C(=O)C(=CC3=CC=C(C4C(F)=CC=CC=4)O3)C(CC3C=CC=CC=3)=N2)=CC=1)O
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| InChi Key |
IZPMWFSVTDOCDI-HAVVHWLPSA-N
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| InChi Code |
InChI=1S/C28H19FN2O4/c29-24-9-5-4-8-22(24)26-15-14-21(35-26)17-23-25(16-18-6-2-1-3-7-18)30-31(27(23)32)20-12-10-19(11-13-20)28(33)34/h1-15,17H,16H2,(H,33,34)/b23-17+
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| Chemical Name |
4-[(4E)-3-benzyl-4-[[5-(2-fluorophenyl)furan-2-yl]methylidene]-5-oxopyrazol-1-yl]benzoic acid
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| Synonyms |
GS143; GS 143; GS-143
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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 : ~37.5 mg/mL (~80.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.46 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 corn oil and mix evenly. Solubility in Formulation 2: 1.88 mg/mL (4.03 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1438 mL | 10.7190 mL | 21.4381 mL | |
| 5 mM | 0.4288 mL | 2.1438 mL | 4.2876 mL | |
| 10 mM | 0.2144 mL | 1.0719 mL | 2.1438 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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