Art. -Nr.: HY-158684

YX-02-030

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YX-02-030 is a VHL-dependent MDM2 PROTAC degrader with a K_d 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)).

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Reinheit: 99.86%
CAS. Nr.: 3049076-98-1
Formel: C₆₆H₈₅Cl₂N₉O₁₀S
Molecular Weight:1267.41

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

YX-02-030 Chemical Structure

CAS. Nr.: 3049076-98-1

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Fluorescent Dye

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

YX-02-030 is a VHL-dependent MDM2 PROTAC degrader with a K_d 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)

Alle PROTACs Isoform-spezifische Produkte anzeigen :

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 K_d 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.

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.

Chemical Information

CAS. Nr. 3049076-98-1
Appearance Solid
Molecular Weight 1267.41
Formel C₆₆H₈₅Cl₂N₉O₁₀S
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

0.7890 mL

3.9451 mL

7.8901 mL

5 mM

0.1578 mL

0.7890 mL

1.5780 mL

10 mM

0.0789 mL

0.3945 mL

0.7890 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

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:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Adams CM, et al. Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer. Cancer Discov. 2023;13(5):1210-1229. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

PROTAC Library

Alle PROTACs Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

YX-02-030 Related Classifications

HY-158684 Related Classifications