2. PROTAC Epigenetics Metabolic Enzyme/Protease Immunology/Inflammation PI3K/Akt/mTOR
  3. PROTACs Histone Acetyltransferase HIF/HIF Prolyl-Hydroxylase PD-1/PD-L1 PTEN
  4. 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)).

For research use only. We do not sell to patients.

NP1192

NP1192 Chemical Structure

CAS No. : 2966791-41-1

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NP1192 Related Antibodies

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HIF-1α HIF

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Description

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))[1].

IC50 & Target[1]

NAT10

 

In Vitro

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.

NP1192 Related Antibodies

Western Blot Analysis[1]

Cell Line: SiHa, U14, and HFF-1 cells
Concentration: 0, 1.25, 2.5, 5, 10 and 20 μM
Incubation Time: 24, 36 and 48 h
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.

Cell Proliferation Assay[1]

Cell Line: SiHa cells and NAT10-KD SiHa cells
Concentration: 20 μM
Incubation Time: 2 weeks
Result: Led to a substantial decrease in colony formation capacity, with the magnitude of inhibition being only second to that in NAT10-knockdown cells.

Cell Invasion Assay[1]

Cell Line: SiHa cells and NAT10-KD SiHa cells
Concentration: 20 μM
Incubation Time: 36 h
Result: Substantially hindered cell invasion with a significant decrease in the number of cells crossing the basement membrane.
In Vivo

NP1192 (25 mg/kg, i.p., every 2 days for a week) synergizes with anti-PD-L1 to inhibit tumor growth, suppress glycolysis, and enhance CD8+ Teff cell immunity in U14-luc xenograft mouse model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female C57BL/6J mice (6-8 weeks old) subcutaneously injected with U14-luc cells[1]
Dosage: 25 mg/kg
Administration: i.p., every 2 days for a week
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.
Molecular Weight

734.87

Formula

C39H42N8O5S
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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NP1192 Related Classifications

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NP11922966791-41-1NP 1192NP-1192PROTACsHistone AcetyltransferaseHIF/HIF Prolyl-HydroxylasePD-1/PD-L1PTENHATsHATHypoxia-inducible factorsHIFsHIF-PHPD-1/Programmed death-ligand 1Phosphatase and tensin homologMMAC1NAT10PROTACac4C modificationhypoxia-driven glycolysisimmunosuppressionHIF-1αPD-L1cervicalCCa cellsovarianglioblastomaTMEInhibitorinhibitorinhibit

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