NP1192
NP1192 is a potent, selective PROTAC NAT10 degrader that depletes NAT10 protein and inhibits ac4C modification in cancer cells. NP1192 demonstrates dual inhibition of hypoxia-driven glycolysis and immunosuppression via NAT10/HIF-1α/PD-L1 axis disruption, achieving superior antitumor efficacy and synergizing with anti-PD-L1 both in vitro and in vivo. NP1192 can be used for ovarian, cervical, and glioblastoma cancer research. (Blue: CRBN ligand (HY-148834); Black: linker; Pink: NAT10 ligand (HY-16706)).
(Pink: NAT10 ligand (HY-16706); Blue: Cereblon ligand (HY-148834); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 2966791-41-1
- Formula: C39H42N8O5S
- Molecular Weight:734.87
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Biological Activity
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NAT10 |
NP1192 (0-20 μM, 24-48 h) induces NAT10 degradation in SiHa (human) and U14 (murine) CCa cell lines in a dose-and time-dependent manner, through the ubiquitin-proteasome system (UPS) rather than via lysosomal pathways[1].
NP1192 (36 h) inhibits cervical cancer (SiHa) cell growth with an IC50 of 7.814 μM (76.2 μM in resistant cells) and additionally shows dose-dependent efficacy in organoids, with IC50 values of 9.947, 3.048, and 13.76 μM for ovarian (OV), cervical (CESC), and glioblastoma (GBM) models, respectively[1].
NP1192 (20 μM, 0-72 h and 2 weeks) significantly reduces cell viability, induces cell cycle arrest, and suppresses invasion and clonogenic growth in CCa cells[1].
NP1192 (0.195-50 μM, 1-8 days) induces a pronounced reduction in organoid size and number across tumor models (ovarian, cervical, and glioblastoma), while the corresponding normal organoids remained unaltered, indicating minimal cytotoxicity to nonmalignant tissues[1].
NP1192 (20 μM, 36 h) reprograms the hypoxic tumor microenvironment (TME) and metabolism in CCa cells by degrading NAT10 and thereby impairing HIF-1α expression, which disrupts glycolysis as evidenced by reduced glucose uptake and lactate production alongside elevated ATP levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SiHa, U14, and HFF-1 cells
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Concentration:0, 1.25, 2.5, 5, 10 and 20 μM
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Incubation Time:24, 36 and 48 h
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Result:Led to a substantial depletion of total NAT10 protein in SiHa (human) and U14 (murine) CCa cell lines in a a dose-and time-dependent manner.
Induced degradation rates of 28%, 32%, 40%, and 43% in SiHa cells at concentrations of 1.25, 2.5, 5, and 10 μM, respectively, with a maximum of 69% degradation at 20 μM after 36 h and only 20% degradation after 24 h.
Led to a nearly 70% reduction in the NAT10 protein content in murine U14 cervical cells after 36 h.
Did not exhibit the classical hook effect even at concentrations as high as 20 μM.
Failed to degrade NAT10 significantly when co-treated with MG132 (HY-13259), whereas Bafilomycin A1 (HY-100558) exerted no discernible effect on its degradation efficacy.
Substantially induced minimal cytotoxicity in nonmalignant HFF-1 cells with low NAT10 expression.
Decreased HIF-1α protein levels.
Reversed the induction of hypoxia-related genes under hypoxic conditions, such as HIF1A and PD-L1, at both mRNA and protein levels.
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Cell Line:SiHa cells and NAT10-KD SiHa cells
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Concentration:20 μM
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Incubation Time:2 weeks
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Result:Led to a substantial decrease in colony formation capacity, with the magnitude of inhibition being only second to that in NAT10-knockdown cells.
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Cell Line:SiHa cells and NAT10-KD SiHa cells
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Concentration:20 μM
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Incubation Time:36 h
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Result:Substantially hindered cell invasion with a significant decrease in the number of cells crossing the basement membrane.
| Species | Dose | Route | Note | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | T1/2 | Tmax | Cmax | F | CL | Vz |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | p.o. | Male SD Rats | 24.7 ng·h/mL | 29.5 ng·h/mL | 1.56 h | 2.85 h | 2.40 h | 1.67 h | 13.9 ng/mL | 1.35 % | / | / |
| Rat[1] | 2 mg/kg | i.v. | Male SD Rats | 365 ng·h/mL | 367 ng·h/mL | 0.529 h | 0.570 h | 0.967 h | 0.0833 h | 759 ng/mL | / | 5.503 L/h/kg | 7.597 L/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6J mice (6-8 weeks old) subcutaneously injected with U14-luc cells[1]
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Dosage:25 mg/kg
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Administration:i.p., every 2 days for a week
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Result:Significantly reduced tumor volume and tumor burden compared to DMSO at 25 mg/kg.
Significantly inhibited tumor growth when combined with anti-PD-L1 antibody (2.5 mg/kg).
Showed the most pronounced reduction (>80%) in tumor lactate levels when combined with anti-PD-L1 antibody (2.5 mg/kg).
¹⁸F-FDG PET–CT imaging revealed minimal metabolic uptake when combined with anti-PD-L1 antibody, suggesting effective suppresses tumor metabolic activity.
Enhanced the CD8+ Teff cell population, reprograms the TME, and potentiates antitumor immunity when combined with anti-PD-L1 blockade.
Did not cause significant weight loss or systemic toxicity both alone and in combination.
Chemical Information
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CAS No. 2966791-41-1
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Molecular Weight 734.87
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Formula C39H42N8O5S
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SMILES
N#CC1=CC=C(C=C1)C2=CSC(N(/N=C3CCCC/3)CCCCCCC(N4CCN(CC4)C5=C6C(N(C(C6=CC=C5)=O)C7CCC(NC7=O)=O)=O)=O)=N2
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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)
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