NP1192
Based on 1 Customer Validation
NP1192 is a potent, selective PROTAC NAT10 degrader. NP1192 promotes NAT10 ubiquitination and degradation. NP1192 inhibits ac4C modification. 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.
(Pink: NAT10 ligand (HY-16706); Blue: Cereblon ligand (HY-148834); Black: linker).
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 99.02%
- CAS 番号: 2966791-41-1
- 分子式: C39H42N8O5S
- 分子量:734.87
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
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NAT10 |
HIF-1α |
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.
化学情報
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CAS 番号 2966791-41-1
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性状 Solid
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分子量 734.87
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
DMSO : 100 mg/mL (136.08 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3608 mL | 6.8039 mL | 13.6078 mL | 34.0196 mL |
| 5 mM | 0.2722 mL | 1.3608 mL | 2.7216 mL | 6.8039 mL | |
| 10 mM | 0.1361 mL | 0.6804 mL | 1.3608 mL | 3.4020 mL | |
| 15 mM | 0.0907 mL | 0.4536 mL | 0.9072 mL | 2.2680 mL | |
| 20 mM | 0.0680 mL | 0.3402 mL | 0.6804 mL | 1.7010 mL | |
| 25 mM | 0.0544 mL | 0.2722 mL | 0.5443 mL | 1.3608 mL | |
| 30 mM | 0.0454 mL | 0.2268 mL | 0.4536 mL | 1.1340 mL | |
| 40 mM | 0.0340 mL | 0.1701 mL | 0.3402 mL | 0.8505 mL | |
| 50 mM | 0.0272 mL | 0.1361 mL | 0.2722 mL | 0.6804 mL | |
| 60 mM | 0.0227 mL | 0.1134 mL | 0.2268 mL | 0.5670 mL | |
| 80 mM | 0.0170 mL | 0.0850 mL | 0.1701 mL | 0.4252 mL | |
| 100 mM | 0.0136 mL | 0.0680 mL | 0.1361 mL | 0.3402 mL |
NP1192 関連分類
HY-178360 関連分類
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