2. PROTAC Apoptosis
  3. PROTACs MDM-2/p53 Apoptosis
  4. YX-02-030

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)).

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

YX-02-030

YX-02-030 Chemical Structure

CAS No. : 3049076-98-1

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

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YX-02-030 Related Antibodies

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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Description

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[1]. (Pink: MDM2 ligand (HY-158685); Blue: VHL ligand (HY-125845); Black: linker (HY-140189)).

IC50 & Target[1]

VHL

 

MDM2

35 nM (Kd)

Cellular Effect
Cell Line Type Value Description References
Breast carcinoma cell IC50
4 μM
Compound: YX-02-030
Antiproliferative activity against human Triple-negative breast cancer cell
Antiproliferative activity against human Triple-negative breast cancer cell
[PMID: 38761584]
In Vitro

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.

YX-02-030 Related Antibodies

Western Blot Analysis[1]

Cell Line: p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells
Concentration: 1, 2, 3, 4, 5, 6, 7, 8 μM
Incubation Time: 4, 8, 10, 12, 14, 16 h
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.

Apoptosis Analysis[1]

Cell Line: p53-mutant MDA-MB-231 and p53-deleted MDA-MB-436 TNBC cells
Concentration: 4 μM
Incubation Time: 24, 48,72 h
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.
In Vivo

YX-02-030 (50 mg/kg; i.p.; daily; 3-14 days) significantly extends survival and reduces tumor volume in MDA-MB-231 and MDA-MB-436 TNBC xenograft mice by inducing tumor cell apoptosis without causing overt toxicity[1].
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.

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]
Dosage: 50 mg/kg
Administration: i.p.; daily; 3 days
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.
Molecular Weight

1267.41

Formula

C66H85Cl2N9O10S
CAS No.
Appearance

Solid

Color

White to off-white

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 0.7890 mL 3.9451 mL 7.8901 mL
5 mM 0.1578 mL 0.7890 mL 1.5780 mL
View the 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.

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In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (1.97 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
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.
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation
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
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YX-02-030 Related Classifications

Help & FAQs
  • 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:

YX-02-0303049076-98-1PROTACsMDM-2/p53ApoptosisMDM2triple negative breast cancerubiquitinationp53TAp73MDA-MB-231proteasome-mediated degradationMDA-MB-436apoptosisVHL E3 ligaseInhibitorinhibitorinhibit

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