NUV-244
NUV-244 is a molecular glue degrader of PNPLA3 I148M. NUV-244 induces degradation via the ubiquitin-proteasome system involving the E3 ligase BFAR. NUV-244 promotes 26S proteasome-dependent degradation of PNPLA3 I148M. NUV-244 restores lipid droplet morphology and cellular fitness in hepatocytes expressing PNPLA3 I148M. NUV-244 can be used in the research of metabolic dysfunction-associated fatty liver disease.
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- Formule: C19H17ClN2O2S
- Masse moléculaire:372.87
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Activité biologique
Description
IC50 & Target
[1]|
PNPLA3 I148M |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| Huh-7 | EC50 |
228 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
365 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
302 nM
|
Restoration of normal lipid droplet morphology and dispersion in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
Restoration of normal lipid droplet morphology and dispersion in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
525 nM
|
Restoration of normal lipid droplet morphology and dispersion in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
Restoration of normal lipid droplet morphology and dispersion in Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
214 nM
|
Reduction of PNPLA3 WT-tagRFP signal at lipid droplets in Huh7 cells expressing PNPLA3 WT-tagRFP by immunofluorescence imaging assay after 24 h incubation.
Reduction of PNPLA3 WT-tagRFP signal at lipid droplets in Huh7 cells expressing PNPLA3 WT-tagRFP by immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
124 nM
|
Reduction of untagged PNPLA3 I148M signal at lipid droplets in Huh7 cells expressing untagged PNPLA3 I148M by immunofluorescence imaging assay after 24 h incubation.
Reduction of untagged PNPLA3 I148M signal at lipid droplets in Huh7 cells expressing untagged PNPLA3 I148M by immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
257 nM
|
Reduction of untagged PNPLA3 WT signal at lipid droplets in Huh7 cells expressing untagged PNPLA3 WT by immunofluorescence imaging assay after 24 h incubation.
Reduction of untagged PNPLA3 WT signal at lipid droplets in Huh7 cells expressing untagged PNPLA3 WT by immunofluorescence imaging assay after 24 h incubation.
|
40322074 |
| HepG2 | EC50 |
296 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in HepG2 cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in HepG2 cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
|
40322074 |
| Hep3B | EC50 |
40 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Hep3B cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in Hep3B cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
|
40322074 |
| LX-2 | EC50 |
188 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in LX-2 hepatic stellate cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in LX-2 hepatic stellate cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
289 nM
|
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in oleic acid-treated Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
Reduction of PNPLA3 I148M-tagRFP signal on lipid droplets in oleic acid-treated Huh7 cells stably expressing PNPLA3 I148M-tagRFP by high-content imaging assay after 24 h incubation.
|
40322074 |
| Huh-7 | EC50 |
199 nM
|
Reduction of total PNPLA3 I148M-HiBiT levels in Huh7 cells stably expressing PNPLA3 I148M-HiBiT by HiBiT luminescence quantification assay after 24 h incubation.
Reduction of total PNPLA3 I148M-HiBiT levels in Huh7 cells stably expressing PNPLA3 I148M-HiBiT by HiBiT luminescence quantification assay after 24 h incubation.
|
40322074 |
In Vitro
NUV-244 (1 μM; 24 h) significantly reduces the levels of PNPLA3I148M on lipid droplets and restores normal lipid droplet morphology in Huh7 cells stably expressing PNPLA3 I148M‑tagRFP[1].
NUV-244 (24 h) significantly reduces the levels of lipid droplet-associated untagged PNPLA3 I148M and untagged wild-type PNPLA3 in Huh7 cells, indicating that its activity does not depend on the presence of the tagRFP fusion tag[1].
NUV-244 (24 h) exhibits activity in multiple liver-derived cell lines, including hepatocellular carcinoma cells and hepatic stellate cells, and retains equivalent potency in cells treated with Oleic acid (HY-N1446) to induce lipid droplet accumulation[1].
NUV-244 (24 h) effectively degrades total intracellular PNPLA3I148M and total PNPLA3 wild-type protein in viable Huh7 cells, confirming that the observed reduction of PNPLA3 signal at lipid droplets corresponds to complete degradation of this protein[1].
NUV-244 (1-5 μM; 0-20 h) triggers a rapid reduction of PNPLA3I148M on lipid droplets in Huh7 cells within 2 hours of administration, with the reduction approaching half of the maximum value[1].
NUV-244 (25 μM) directly and selectively binds to purified PNPLA3 WT and PNPLA3 I148M proteins in a cell-free assay, and no interaction with PNPLA2 is detected[1].
NUV-244 (24 h) effectively reduces the PNPLA3I148M protein level in differentiated adipocytes, with an EC50 of 2.02 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Huh7 cells stably expressing PNPLA3 I148M-tagRFP
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Concentration:1, 5 μM
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Incubation Time:0-20 h
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Result:Induces rapid reduction of PNPLA3 I148M-tagRFP intensity on lipid droplets, reaching half-maximal effect at approximately 2 hours post-incubation.
Chemical Information
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Masse moléculaire 372.87
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Formule C19H17ClN2O2S
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SMILES
CC1=CC(CC2=NC(C)=C(C(NC3=CC(O)=CC=C3Cl)=O)S2)=CC=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)