NUAK1-IN-3
NUAK1-IN-3 is a potent and selective NUAK1 inhibitor with an IC50 of 0.49 nM. NUAK1-IN-3 also inhibits NUAK2 and JAK3 with IC50 values of 265 and 225 nM. NUAK1-IN-3 engages Glu139 of NUAK1, forms a salt bridge between its bicyclic ring nitrogen and Asp142, and uses a fluorine atom to enhance hydrophobic binding interactions. NUAK1-IN-3 attenuates MYPT1 phosphorylation, suppresses the NUAK1-MYPT1 signaling axis, and inhibits proliferation, migration, and invasion of triple-negative breast cancer cells. NUAK1-IN-3 reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) marker alterations, downregulates Snail and N-cadherin, and upregulates E-cadherin in tumor tissues. NUAK1-IN-3 suppresses tumor growth in triple-negative breast cancer xenograft models. NUAK1-IN-3 can be used for the research of triple-negative breast cancer.
For research use only. We do not sell to patients.
- CAS No.: 3097515-05-1
- Formula: C30H35ClFN7O6
- Molecular Weight:644.09
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Biological Activity
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Chemical Information
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All AMPK Isoforms
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Biological Activity
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NUAK1 0.49 nM (IC50) |
JAK3 225 nM (IC50) |
NUAK2 265 nM (IC50) |
NUAK1-IN-3 (Compound 10i) potently inhibits NUAK1 with an IC50 of 0.49 nM, and exhibits 459-fold and 541-fold selectivity over JAK3 (IC50 = 225 nM) and NUAK2 (IC50 = 265 nM) , respectively[1].
NUAK1-IN-3 (0-50 μM; 96 h) inhibits proliferation of BT549 and MDA-MB-231 triple-negative breast cancer cells with IC50 values of 2.8 μM and 3.4 μM, respectively[1].
NUAK1-IN-3 (1000-10000 nM; 16 h) dose-dependently attenuates MYPT1 phosphorylation in BT549 and MDA-MB-231 triple-negative breast cancer cells[1].
NUAK1-IN-3 (1-5 μM; 24 h) dose-dependently inhibits migration of BT549 and MDA-MB-231 triple-negative breast cancer cells[1].
NUAK1-IN-3 (3-10 μM; 24 h) dose-dependently inhibits invasion of BT549 and MDA-MB-231 triple-negative breast cancer cells, with 10 μM showing efficacy comparable to siRNA-mediated NUAK1 knockdown[1].
NUAK1-IN-3 (1-10 μM; 24 h) dose-dependently inhibits the EMT pathway in BT549 and MDA-MB-231 triple-negative breast cancer cells by downregulating N-cadherin and Snail expression in the presence of TGF-β1[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human triple-negative breast cancer BT549 cells, human triple-negative breast cancer MDA-MB-231 cells
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Concentration:1000, 3000, 5000, 10000 nM
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Incubation Time:16 h
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Result:Dose-dependently reduced phosphorylation of MYPT1 (Ser668) in both BT549 and MDA-MB-231 cells.
Confirmed direct NUAK1 target engagement and inhibition of the NUAK1-MYPT1 signaling axis.
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Cell Line:human triple-negative breast cancer BT549 cells, human triple-negative breast cancer MDA-MB-231 cells
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Concentration:1, 5, 10 μM (in the presence of 20 ng/mL TGF-β1)
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Incubation Time:24 h
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Result:Dose-dependently downregulated the expression of EMT markers N-cadherin and Snail in both BT549 and MDA-MB-231 cells.
Reversed TGF-β1-induced EMT alterations.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-∞ | CL | Vss | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 0.85 h | 0.03 h | 581 ng/mL | 204 ng·h/mL | 206 ng·h/mL | 0.64 h | 161 mL/min/kg | 6.20 L/kg | / |
| Mice[1] | 6 mg/kg | p.o. | 1.69 h | 0.08 h | 45.6 ng/mL | 96.6 ng·h/mL | 103 ng·h/mL | 2.37 h | / | / | 16.6 % |
| Mice[1] | 60 mg/kg | p.o. | 1.21 h | 0.194 h | 809 ng/mL | 768 ng·h/mL | 783 ng·h/mL | 1.52 h | / | / | 12.6 % |
| Mice[1] | 60 mg/kg | i.p. | 0.773 h | 0.194 h | 7177 ng/mL | 5947 ng·h/mL | 5950 ng·h/mL | 0.620 h | / | / | 95.9 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCG mice (female, 4 weeks old, triple-negative breast cancer subcutaneous xenograft model)[1]
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Dosage:60 mg/kg; 100 mg/kg
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Administration:i.p.; daily; 16 days
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Result:Achieved 70.93% tumor growth inhibition (TGI) at 60 mg/kg.
Achieved 83.55% TGI at 100 mg/kg.
Significantly reduced tumor volumes and weights relative to vehicle control at both doses.
Increased E-cadherin expression in tumor sections relative to vehicle control.
Reduced N-cadherin expression in tumor sections relative to vehicle control.
Caused no overt toxicity, significant body weight loss, or histopathological abnormalities in heart, liver, spleen, or kidneys.
Chemical Information
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CAS No. 3097515-05-1
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Molecular Weight 644.09
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Formula C30H35ClFN7O6
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SMILES
[H][C@@]12[C@@H](CO[C@@]1([C@@H](CO2)OC3=NC(NC4=CC=C(C(NC(C5=CN(N=C5)C)=O)=C4)OC[C@@]67CCCN6C[C@@H](C7)F)=NC=C3Cl)[H])OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NUAK1-IN-3 Related Classifications
HY-182361 Related Classifications
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