| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Intermediate for NAT10 PROTAC NP1192
Remodelin-C6-COOH targets N-acetyltransferase 10 (NAT10), an enzyme that catalyzes N4-acetylcytidine (ac4C) modification on RNA and also possesses protein acetyltransferase activity. As a ligand-linker conjugate, the compound retains the NAT10-binding properties of Remodelin while providing a functionalized handle for conjugation to E3 ligase ligands. When incorporated into a complete PROTAC molecule such as NP1192, the targeting moiety directs the ubiquitin-proteasome system to degrade NAT10 protein rather than simply inhibiting its enzymatic activity. NAT10 has emerged as an attractive anticancer target due to its role in promoting hypoxia-driven glycolysis and immunosuppression in the tumor microenvironment. |
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| ln Vitro |
Synthetic procedure:
Remodelin-C6-COOH or Intermediate 3 (1 g, 3.54 mmol), methyl 7-bromoheptanoate (1.19 g, 5.31 mmol) and potassium carbonate (1.47 g, 10.62 mmol) were dissolved in 5 mL DMF, the mixture was stirred at room temperature for 12 h. After the reaction completed, the mixture was extracted with ethyl acetate. The organic layer was collected and evaporated under reduced pressure and purified by column chromatography with petroleum ether / ethyl acetate (10:1) to give a white oil intermediate. The intermediate was dissolved in 36 mL methanol, sodium hydroxide solution (10.0 equiv, dissolved in 4 mL of H2O) was added. The reaction solution was stirred at room temperature for 1 h. After the reaction was completed, the solvent was concentrated in vacuo, then the water and 3M HCl was added to adjust the pH of the solution to 4-6, the residue was extracted with ethyl acetate and evaporated under reduced pressure to obtain white oil 4 (65.0 %). [1] In vitro activity of Remodelin-C6-COOH is primarily characterized through its ability to bind NAT10, as assessed by biophysical and biochemical assays. The compound retains the NAT10 inhibitory activity of the parent Remodelin molecule, though its potency may be somewhat reduced due to the linker attachment. Standard assays for NAT10 inhibition measure the reduction of ac4C RNA modification levels in treated cells or the inhibition of NAT10 enzymatic activity in vitro using acetyl-CoA and substrate RNA or peptide. When used as a building block for PROTAC synthesis, the resulting degrader NP1192 demonstrates significantly enhanced antiproliferative activity compared to the parent inhibitor, achieving nearly 70% NAT10 degradation in cancer cells. |
| ln Vivo |
In vivo activity of Remodelin-C6-COOH as a standalone compound has not been extensively characterized, as it is primarily a synthetic intermediate rather than a therapeutic agent. However, the complete PROTAC degrader NP1192, which incorporates this ligand-linker conjugate, demonstrates superior antitumor efficacy compared to Remodelin alone in various preclinical models. NP1192 exhibits dual inhibition of hypoxia-driven glycolysis and immunosuppression via disruption of the NAT10/HIF-1α/PD-L1 axis, achieving potent antitumor effects in cervical cancer models and synergizing with anti-PD-L1 immunotherapy. These in vivo findings validate the utility of the Remodelin ligand-linker scaffold for targeted NAT10 degradation.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Remodelin-C6-COOH typically measure its ability to inhibit NAT10 acetyltransferase activity using biochemical reconstitution systems. Recombinant NAT10 enzyme is incubated with acetyl-CoA and a suitable substrate (RNA or peptide) in the presence of varying concentrations of the test compound. The reaction progress is monitored by detection of acetylated product using radiolabeled acetyl-CoA, antibody-based detection, or mass spectrometry. Inhibition curves are generated to calculate IC50 values. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) may be employed to directly measure binding affinity (Kd) between Remodelin-C6-COOH and NAT10. Competition binding assays using fluorescently labeled Remodelin can also assess relative binding potency.
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| Cell Assay |
In vitro cellular assays for Remodelin-C6-COOH are typically performed in cancer cell lines to evaluate NAT10 target engagement and functional consequences. Cells are treated with the compound for 24-72 hours, and NAT10 activity is assessed by measuring ac4C RNA modification levels using ac4C-specific antibodies in RNA immunoprecipitation (ac4C-RIP) or by LC-MS/MS nucleoside analysis. Cell viability and proliferation are measured using standard assays such as MTT, CCK-8, or colony formation. For compounds incorporating the Remodelin-C6-COOH scaffold into a complete PROTAC (e.g., NP1192), NAT10 protein degradation is confirmed by Western blot, and downstream effects on HIF-1α and PD-L1 expression are evaluated.
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| Animal Protocol |
In vivo animal studies using Remodelin-C6-COOH as a standalone compound are not typically performed, as it is a synthetic intermediate rather than a finished therapeutic agent. However, the complete PROTAC degrader NP1192, synthesized from this ligand-linker conjugate, has been evaluated in mouse xenograft models of cervical cancer and other tumor types. In these studies, NP1192 is administered via intraperitoneal or intravenous injection at various doses, and tumor growth inhibition, body weight, and survival are monitored. Pharmacodynamic endpoints include assessment of NAT10 degradation, ac4C modification levels, and immune cell infiltration in tumor tissues. Combination studies with anti-PD-L1 antibodies have demonstrated synergistic antitumor efficacy.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Remodelin-C6-COOH as an individual compound have not been extensively reported, as it is primarily a synthetic building block rather than a drug candidate. However, the complete PROTAC degrader NP1192, derived from this ligand-linker conjugate, likely exhibits typical properties of small-molecule PROTACs including moderate molecular weight, potential for oral bioavailability depending on formulation, and clearance via hepatic metabolism. The carboxylic acid functionality may influence plasma protein binding and tissue distribution. For the parent compound Remodelin, studies indicate moderate cell permeability and metabolic stability, though comprehensive PK data in animal models are limited.
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| Toxicity/Toxicokinetics |
Toxicological data for Remodelin-C6-COOH as a standalone compound are not available in public literature, consistent with its status as a research intermediate rather than a therapeutic agent. The parent molecule Remodelin has been studied in cellular models and shows manageable cytotoxicity profiles at concentrations used for NAT10 inhibition. For the complete PROTAC degrader NP1192 incorporating this scaffold, preclinical toxicology would need to address potential off-target degradation effects, immune-related toxicities, and organ-specific accumulation. As with all PROTAC molecules, the potential for ubiquitin-proteasome system saturation and associated cellular stress responses represents a theoretical safety consideration.
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| References | |
| Additional Infomation |
Remodelin-C6-COOH is a synthetic ligand-linker conjugate used as a key intermediate for assembling NP1192, a potent PROTAC degrader targeting NAT10. Its mechanism, when incorporated into a complete PROTAC, involves recruiting NAT10 to E3 ubiquitin ligases for ubiquitination and proteasomal degradation. This degradation strategy disrupts the NAT10/HIF-1α/PD-L1 axis, achieving dual inhibition of hypoxia-driven glycolysis and immunosuppression. NP1192 shows superior antitumor efficacy compared to Remodelin alone and synergizes with anti-PD-L1 immunotherapy. No clinical trials or regulatory approvals exist for this research intermediate.
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| Molecular Formula |
C22H26N4O2S
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|---|---|
| Molecular Weight |
410.53
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| CAS # |
2966791-35-3
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| Appearance |
Typically exists as solids at room temperature
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| Chemical Name |
7-(1-(4-(4-cyanophenyl)thiazol-2-yl)-2-cyclopentylidenehydrazineyl)heptanoic acid (4)
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4359 mL | 12.1794 mL | 24.3588 mL | |
| 5 mM | 0.4872 mL | 2.4359 mL | 4.8718 mL | |
| 10 mM | 0.2436 mL | 1.2179 mL | 2.4359 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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