YX-02-030
Based on 1 Customer Validation
YX-02-030 is a VHL-dependent MDM2 PROTAC degrader with a Kd of 35 nM. YX-02-030 recruits the VHL E3 ligase to form a ternary complex, leading to ubiquitination and proteasome-mediated degradation of MDM2. YX-02-030 inhibits MDM2-p53 and VHL-HIF1α binding with IC50 values of 63 and 1350 nM. YX-02-030 activates TAp73, upregulates p53 family target genes and induces apoptosis. YX-02-030 demonstrates on-target efficacy in TNBC xenograft-bearing mice, extending survival without normal cell toxicity.
(Pink: MDM2 ligand (HY-158685); Blue: VHL ligand (HY-125845); Black: linker (HY-140189)).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity: 99.86%
- CAS No.: 3049076-98-1
- 화학식: C66H85Cl2N9O10S
- 분자량:1267.41
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
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VHL |
MDM2 35 nM (Kd) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Breast carcinoma cell | IC50 |
4 μM
Compound: YX-02-030
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Antiproliferative activity against human Triple-negative breast cancer cell
Antiproliferative activity against human Triple-negative breast cancer cell
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[PMID: 38761584] |
YX-02-030 potently inhibits MDM2-p53 binding in a cell-free HTRF assay with an IC50 of 63 nM[1].
YX-02-030 inhibits VHL-HIF1α binding in a cell-free HTRF assay with an IC50 of 1350 nM[1].
YX-02-030 (1-1000 nM) binds purified MDM2 protein with high affinity in a cell-free SPR assay, having an equilibrium Kd of 35 nM[1].
YX-02-030 (1-10000 nM) efficiently forms a ternary complex between purified MDM2 and VHL proteins in a cell-free AlphaScreen assay[1].
YX-02-030 (1-8 μM; 4-16 h) induces concentration- and time-dependent 26S proteasome-mediated degradation of MDM2 in p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells, a process requiring ubiquitin cascade function and ternary complex formation with VHL[1].
YX-02-030 (0.1-10 μM; 48 h) reduces survival of p53-wildtype MCF7 and DU4475 breast cancer cells with IC50 values of 2.8 μM and 2.3 μM[1].
YX-02-030 (3 μM) induces apoptosis in p53-wildtype MCF7 breast cancer cells via activation of p53 and its pro-apoptotic target genes[1].
YX-02-030 (4 μM; 72 h) inhibits mammosphere formation and induces apoptosis in pre-formed mammospheres of p53-wildtype MCF7 breast cancer cells in 3D culture[1].
YX-02-030 (0.1-10 μM; 48 h) reduces survival of p53-mutant (MDA-MB-231, HCC-1143, HCC-1395) and p53-deleted (MDA-MB-436, MDA-MB-453) TNBC cells with IC50 values of 4.0-5.5 μM[1].
YX-02-030 (4 μM; 24-72 h) induces time-dependent apoptosis in p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells[1].
YX-02-030 (1-2 μM; 12 days) reduces clonogenic potential of p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells[1].
YX-02-030 (0.5-6 μM; 72 h) inhibits mammosphere formation and induces apoptosis in pre-formed mammospheres of p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells in 3D culture[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells
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Concentration:1, 2, 3, 4, 5, 6, 7, 8 μM
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Incubation Time:4, 8, 10, 12, 14, 16 h
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Result:Induced concentration- and time-dependent loss of MDM2 protein in both cell lines, with no change in VHL protein levels.
Blocked MDM2 degradation via pre-treatment with MLN4924 (HY-70062), MG132 (HY-13259), RG7112 (HY-10959), VHL-Amine, or VH298 (HY-100947).
Left MDM2 mRNA levels unchanged following treatment.
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Cell Line:p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells
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Concentration:4 μM
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Incubation Time:24, 48,72 h
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Result:Induced time-dependent increases in Annexin-V positivity, Caspase-3 activity, subG1 apoptotic DNA content, and cleaved PARP levels in both cell lines.
Blocked cleaved PARP induction via pre-treatment with MG132, VHL-Amine, or VH298.
YX-02-030 (50 mg/kg; i.p.; daily; 3 days) does not activate p53-mediated apoptotic pathways in normal C57BL/6 mouse hematopoietic cells and causes no overt toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic nude mice (6-8 week-old female; subcutaneous xenograft of MDA-MB-231 and MDA-MB-436 p53-mutant TNBC cells)[1]
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Dosage:50 mg/kg
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Administration:i.p.; daily; 3 days
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Result:Significantly extended mouse survival compared to vehicle control.
Significantly reduced tumor volume over time.
Induced loss of MDM2 protein, increased cleaved PARP Annexin-V positivity, Caspase-3 activity, apoptotic subG1 DNA content, and non-viable cells in tumors.
Caused no overt toxicity, with maintained mouse weight, normal complete blood counts, and normal histology of spleen, bone marrow, and intestine.
Chemical Information
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CAS No. 3049076-98-1
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Appearance Solid
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분자량 1267.41
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화학식 C66H85Cl2N9O10S
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Color White to off-white
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SMILES
O=C(CN1CCN(C(N2[C@](C)(C3=CC=C(Cl)C=C3)[C@](C)(C4=CC=C(Cl)C=C4)N=C2C5=CC=C(C(C)(C)C)C=C5OCC)=O)CC1)NCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N6[C@H](C(NCC7=CC=C(C8=C(C)N=CS8)C=C7)=O)C[C@@H](O)C6)=O)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 100 mg/mL (78.90 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.
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: ≥ 2.5 mg/mL (1.97 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
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.
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.
순도&문서
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Data Sheet (279 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
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 | 0.7890 mL | 3.9451 mL | 7.8901 mL | 19.7253 mL |
| 5 mM | 0.1578 mL | 0.7890 mL | 1.5780 mL | 3.9451 mL | |
| 10 mM | 0.0789 mL | 0.3945 mL | 0.7890 mL | 1.9725 mL | |
| 15 mM | 0.0526 mL | 0.2630 mL | 0.5260 mL | 1.3150 mL | |
| 20 mM | 0.0395 mL | 0.1973 mL | 0.3945 mL | 0.9863 mL | |
| 25 mM | 0.0316 mL | 0.1578 mL | 0.3156 mL | 0.7890 mL | |
| 30 mM | 0.0263 mL | 0.1315 mL | 0.2630 mL | 0.6575 mL | |
| 40 mM | 0.0197 mL | 0.0986 mL | 0.1973 mL | 0.4931 mL | |
| 50 mM | 0.0158 mL | 0.0789 mL | 0.1578 mL | 0.3945 mL | |
| 60 mM | 0.0132 mL | 0.0658 mL | 0.1315 mL | 0.3288 mL |
YX-02-030 Related Classifications
HY-158684 Related Classifications
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