P62-RNF168 agonist-1
Based on 1 Customer Validation
P62-RNF168 agonist-1 (compound 5a) is a low cytotoxicity P62-RNF168 agonist that enhances the interaction between P62 and RNF168. P62-RNF168 agonist-1 induces a reduction in H2A ubiquitination mediated by RNF168 and impairs homologous recombination-mediated DNA repair. P62-RNF168 agonist-1 also inhibits the growth of xenograft tumors in mice in a dose-dependent manner.
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- Pureté: 98.03%
- CAS No.: 2765180-17-2
- Formule: C19H19N7O3
- Masse moléculaire:393.40
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Stockage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-375 | IC50 |
1.93 μM
Compound: 5a
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Cytotoxicity against human A-375 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human A-375 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| A549 | IC50 |
1.18 μM
Compound: 5a
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Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| HCT-116 | IC50 |
0.36 μM
Compound: 5a
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Cytotoxicity against human HCT-116 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human HCT-116 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| HeLa | IC50 |
2.48 μM
Compound: 5a
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Cytotoxicity against human HeLa cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human HeLa cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| HepG2 | IC50 |
19.61 μM
Compound: 5a
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Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| MCF-10A | IC50 |
6.98 μM
Compound: 5a
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Cytotoxicity against human MCF-10A cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human MCF-10A cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| MCF7 | IC50 |
2.79 μM
Compound: 5a
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Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| MDA-MB-231 | IC50 |
1.17 μM
Compound: 5a
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Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| MGC-803 | IC50 |
1.88 μM
Compound: 5a
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Cytotoxicity against human MGC-803 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human MGC-803 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
| U2OS | IC50 |
3.64 μM
Compound: 5a
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Cytotoxicity against human U2OS cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Cytotoxicity against human U2OS cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 36331508] |
P62-RNF168 agonist-1 (20 μM, 72 h) has an IC50 of 0.36 μM for the cancer cell line HCT116 and an IC50 of 1.18 μM for A549. It shows cytotoxicity against cancer cells A357, HeLa, HepG2, MCF-7, MDA-MB-231, MGC-803, and H2OS, but does not induce cell apoptosis and has lower toxicity towards normal cells MCF-10A[1].
P62-RNF168 agonist-1 (1-5 μM; 24 h) affects the HR (homologous recombination)-mediated DSB repair in HCT-116 cells, contributing to its antitumor activity[1].
P62-RNF168 agonist-1 enhances the interaction between P62 and RNF168 in HCT-116 cells, with a Kd of 20.97 μM[1].
P62-RNF168 agonist-1 inhibits the catalytic activity of RNF168 and the E3 ligase activity of RNF168 in HCT-116 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549, HCT-116, A375, HeLa, HepG2, MCF-7, MDA-MB-231, MGC-803, U2OS and MCF-10A cells
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Concentration:0-20 µM
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Incubation Time:72 h
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Result:Inhibited A549, HCT-116, A375, HeLa, HepG2, MCF-7, MDA-MB-231, MGC-803, U2OS and MCF-10A cells, with IC50 values of 1.18, 0.36, 1.93, 2.48, 19.61, 2.79, 1.17, 1.88, 3.64 and 6.98, respectively.
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Cell Line:HCT-116 cells
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Concentration:1, 2, 5 µM
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Incubation Time:24 h
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Result:Induced a G2/M arrest but no significant accumulation of sub-G1 phase.
Compromised both HR(homologous recombination)- and NHEJ (non-homologous end joining)- mediated DSB repair in a dose-dependent manner, but HR was the more severely impacted process.
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Cell Line:HCT-116
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Concentration:10 µM
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Incubation Time:Over night
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Result:Had the expression of RNF168 and GST-RNF168 ,increased the level of P62 in the endogenous RNF-168 immune complex.
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Cell Line:HCT-116
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Concentration:5, 10 µM
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Incubation Time:24 h
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Result:Made apoptosis less obvious.
P62-RNF168 agonist-1 (5-10 mg/kg, i.p., single every 3 days for 22 days) promotes tumor apoptosis and inhibits tumor growth in mice[1].
| Dose | T1/2 (h) | Cmax (ng/mL) | AUC0-t (h?ng/mL) | CL ((mL/h)/kg) |
| IP (5 mg/kg) | 16.17 | 26.10 | 215.69 | 19647.83 |
| IP (10 mg/kg) | 31.00 | 39.87 | 408.18 | 16554.30 |
| IP (20 mg/kg) | 22.10 | 52.23 | 1003.58 | 14669.81 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (xenograft tumor model)[1].
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Dosage:5, 10 mg/kg
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Administration:Intraperitoneal injection; single every 3 days for 22 days
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Result:Suppressed tumor growth by promoting apoptosis in xenografted tumorigenesis.
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Animal Model:Female BALB/c nude mice[1].
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Dosage:5, 10, 20 mg/kg
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Administration:Intraperitoneal injection; single
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Result:Exhibited plasma concentration peaked 1 h after administration.
Showed a relatively high maximum concentration (Cmax= 52.23 ng/mL) and exposure (AUC0-t= 1003.58 h•ng/mL) at a dose of 20 mg/kg.
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Animal Model:BALB/c mice, Female nude mice[1]
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Dosage:25, 50, 75, 100 mg/kg, single dose; 12.5, 25, 50 mg/kg, single dose
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Administration:Intraperitoneal injection
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Result:Showed in the 100 mg/kg dosage group of BALB/c mice, out of 8 animals, 3 males and 3 females died on the 7th day, and the remaining animals experienced diarrhea. In the 75 mg/kg dosage group, 1 out of 8 animals (1 male) had diarrhea on the 7th day. There were no deaths or diarrhea observed in the ≤50 mg/kg dosage group.
Showed in the female nude mice, both the 25 and 50 mg/kg dosage groups experienced deaths or diarrhea, while the 12.5 mg/kg dosage group had no deaths or diarrhea.
Chemical Information
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CAS No. 2765180-17-2
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Appearance Solid
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Masse moléculaire 393.40
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Formule C19H19N7O3
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Color Off-white to light yellow
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SMILES
NC1=C2C(C=CC(C3=CN(C4=CC(OC)=C(C(OC)=C4)OC)N=N3)=C2)=NC(N)=N1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvant et solubilité
DMSO : ≥ 60 mg/mL (152.52 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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 (protect from light). 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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.4 mg/mL (6.10 mM); Clear solution
This protocol yields a clear solution of ≥ 2.4 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (24.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.4 mg/mL (6.10 mM); Clear solution
This protocol yields a clear solution of ≥ 2.4 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (24.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
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 (protect from light). 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 | 2.5419 mL | 12.7097 mL | 25.4194 mL | 63.5486 mL |
| 5 mM | 0.5084 mL | 2.5419 mL | 5.0839 mL | 12.7097 mL | |
| 10 mM | 0.2542 mL | 1.2710 mL | 2.5419 mL | 6.3549 mL | |
| 15 mM | 0.1695 mL | 0.8473 mL | 1.6946 mL | 4.2366 mL | |
| 20 mM | 0.1271 mL | 0.6355 mL | 1.2710 mL | 3.1774 mL | |
| 25 mM | 0.1017 mL | 0.5084 mL | 1.0168 mL | 2.5419 mL | |
| 30 mM | 0.0847 mL | 0.4237 mL | 0.8473 mL | 2.1183 mL | |
| 40 mM | 0.0635 mL | 0.3177 mL | 0.6355 mL | 1.5887 mL | |
| 50 mM | 0.0508 mL | 0.2542 mL | 0.5084 mL | 1.2710 mL | |
| 60 mM | 0.0424 mL | 0.2118 mL | 0.4237 mL | 1.0591 mL | |
| 80 mM | 0.0318 mL | 0.1589 mL | 0.3177 mL | 0.7944 mL | |
| 100 mM | 0.0254 mL | 0.1271 mL | 0.2542 mL | 0.6355 mL |
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