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Cat. No.: HY-162450

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PROTAC MDM2 Degrader-8

PROTAC MDM2 Degrader-8 is a PROTAC degrader that induces the degradation of the MDM2 protein by recruiting VHL. PROTAC MDM2 Degrader-8 directly binds to MDM2 with a K_D of 38.2 μM; the proteasome inhibitor MG-132 (HY-13259) reverses this degradation effect, supporting that it induces MDM2 degradation via the ubiquitin-proteasome system. PROTAC MDM2 Degrader-8 also upregulates p21, induces apoptosis and cell cycle arrest, and inhibits the migration of MDA-MB-231 cells. PROTAC MDM2 Degrader-8 can be used in studies related to MDM2-targeted protein degradation and triple-negative breast cancer.
(Pink: MDM-2/p53 and MDM-2 ligand (HY-N1447); Blue: VHL ligand (HY-112078); Black: linker).

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

화학식: C₇₀H₁₀₆N₈O₁₄S
분자량:1315.70

보관:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (282 KB)

PROTAC MDM2 Degrader-8 Chemical Structure

Amount: USD 0.00

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

PROTAC MDM2 Degrader-8 is a PROTAC degrader that induces the degradation of the MDM2 protein by recruiting VHL. PROTAC MDM2 Degrader-8 directly binds to MDM2 with a K_D of 38.2 μM; the proteasome inhibitor MG-132 (HY-13259) reverses this degradation effect, supporting that it induces MDM2 degradation via the ubiquitin-proteasome system. PROTAC MDM2 Degrader-8 also upregulates p21, induces apoptosis and cell cycle arrest, and inhibits the migration of MDA-MB-231 cells. PROTAC MDM2 Degrader-8 can be used in studies related to MDM2-targeted protein degradation and triple-negative breast cancer^[1]. (Pink: MDM-2/p53 and MDM-2 ligand (HY-N1447); Blue: VHL ligand (HY-112078); Black: linker).

IC₅₀ & Target

^[1]

MDM2

38.2 μM (Kd)

All PROTACs Isoforms :

In Vitro

The cell viability of PROTAC MDM2 Degrader-8 (compound V10) (100 μM) in MCF-7, MDA-MB-231, SJSA-1, HepG2, and HT-22 cells is 30.6%, 16.9%, 61.3%, 92.9%, and 91.3% of that in the control group, respectively; among these, the proliferation inhibition rate in MDA-MB-231 cells is 83.1%^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces MDM2 protein levels in a concentration-dependent manner in p53-mutant MDA-MB-231 cells, with a maximum MDM2 degradation rate of 51% at 80 μM^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces the BCL-2/BAX ratio in MDA-MB-231 cells^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) inhibits the migration of MDA-MB-231 cells; at 80 μM, the migration inhibition rates at 24 h and 48 h are 55% and 69%, respectively^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) upregulates p21 protein levels concomitant with the reduction of MDM2 in MDA-MB-231 cells^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) upregulates p21 mRNA and reduces Cyclin B1 protein expression in MDA-MB-231 cells^[1].
PROTAC MDM2 Degrader-8 (80 μM; 48 h) increases the proportion of cells in the G1 and G2 phases while decreasing the proportion of cells in the S phase in MDA-MB-231 cells, which manifests as G1-S and G2-M cell cycle arrest^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) increases p21 signaling in MDA-MB-231 cells in immunofluorescence assays^[1].
MDM2 degradation induced by PROTAC MDM2 Degrader-8 (80 μM; 48 h) is reversed by MG-132 (30 μM; 2 h pre-exposure), while equivalent concentrations of GAA or VHL ligand alone fail to reduce MDM2 protein levels, supporting the necessity of intact PROTAC structure and the proteasome for MDM2 degradation^[1].
PROTAC MDM2 Degrader-8 (3.13-100 μM; MDM2 protein 50 μg/mL; binding 400 s; dissociation 60 s) directly binds to MDM2 in SPR assays, with a K_D of 38.2 μM^[1].
PROTAC MDM2 Degrader-8 (30 min) enhances the thermal stability of MDM2 in CETSA, further supporting target engagement of MDM2 in cell-derived systems^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) reduces MDM2 signaling in MDA-MB-231 cells in immunofluorescence assays^[1].
PROTAC MDM2 Degrader-8 (20-80 μM; 48 h) induces apoptosis in MDA-MB-231 cells, with the apoptosis rate reaching 48.39% at 80 μM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

V10: 80 μM; GAA: 80 μM; VHL ligand: 80 μM; MG-132: 30 μM
Incubation Time:

48 h; 2 h (MG-132 pre-treatment)
Result:

Decreased MDM2 protein levels.
GAA alone did not decrease MDM2 protein levels.
The VHL ligand alone did not decrease MDM2 protein levels.
MG-132 reversed MDM2 degradation.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

20, 40, 80 μM
Incubation Time:

48 h
Result:

Decreased MDM2 protein levels in a concentration-dependent manner.
Reached 51% MDM2 degradation at 80 μM.
Increased p21 protein levels.
Decreased the BCL-2/BAX ratio.
Decreased Cyclin B1 protein expression.

Apoptosis Analysis^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

20, 40, 80 μM
Incubation Time:

48 h
Result:

Increased apoptosis.
Produced an apoptotic rate of 48.39% at 80 μM.

Cell Migration Assay ^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

20, 40, 80 μM
Incubation Time:

24 h, 48 h
Result:

Inhibited migration by 55% at 24 h at 80 μM.
Inhibited migration by 69% at 48 h at 80 μM.

Cell Cycle Analysis^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

20, 40, 80 μM
Incubation Time:

48 h
Result:

Increased the G1-phase population at 80 μM.
Decreased the S-phase population at 80 μM.
Increased the G2-phase population at 80 μM.
Produced G1-S and G2-M cell-cycle arrest.

RT-PCR^[1]

Cell Line:

MDA-MB-231 human triple-negative breast cancer cells
Concentration:

20, 40, 80 μM
Incubation Time:

48 h
Result:

Increased p21 mRNA expression.

In Vivo

PROTAC MDM2 Degrader-8 (compound V10) (6.25-100 μg/mL; aqueous solution exposure; 2 days) causes no death or obvious toxic phenotypes in 3 dpf wild-type AB zebrafish at concentrations of 6.25-50 μg/mL, whereas 4 out of 30 zebrafish die at 100 μg/mL, corresponding to a mortality rate of 13%; the MTC is determined to be 50 μg/mL^[1].
PROTAC MDM2 Degrader-8 (12.5-50 μg/mL; aqueous solution exposure; 2 days) produces tumor growth inhibition rates of 16.8%, 23.4%, and 27.2%, respectively, in the MDA-MB-231 TNBC xenograft zebrafish model; the inhibition rate of the 15 μg/mL Cisplatin (HY-17394) positive control group is 33.2%^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

3-dpf zebrafish^[1]
Dosage:

6.25 μg/mL, 12.5 μg/mL, 25 μg/mL, 50 μg/mL, 100 μg/mL
Administration:

waterborne; continuous; 2 day exposure
Result:

Caused no mortality at 6.25, 12.5, 25, or 50 μg/mL.
Produced no apparent toxic phenotype at 6.25-50 μg/mL.
Caused 4 deaths among 30 zebrafish at 100 μg/mL.
Produced a mortality rate of 13% at 100 μg/mL.
Established an MTC of 50 μg/mL.

Animal Model:

2-dpf zebrafish; approximately 200 CM-DiI-labeled MDA-MB-231 cells microinjected into the yolk sac; model selected at 3 dpf^[1]
Dosage:

12.5, 25, 50 μg/mL
Administration:

waterborne; continuous; 2 day exposure
Result:

Inhibited xenograft tumor growth by 16.8% at 12.5 μg/mL.
Inhibited xenograft tumor growth by 23.4% at 25 μg/mL.
Inhibited xenograft tumor growth by 27.2% at 50 μg/mL.
The 15 μg/mL cisplatin positive-control group produced 33.2% inhibition.

Related Protocols :

Chemical Information

분자량 1315.70
화학식 C₇₀H₁₀₆N₈O₁₄S
SMILES

O=C1C[C@@]2(C)[C@]([C@@H](O)C[C@@H]2[C@H](C)CC(C[C@@H](C)C(NCCOCCOCCOCCOCCN3CC(CCCCC(N[C@@H](C(C)(C)C)C(N4C[C@H](O)C[C@H]4C(N[C@@H](C)C5=CC=C(C6=C(C)N=CS6)C=C5)=O)=O)=O)N=N3)=O)=O)(C)C7=C1[C@]8(C)[C@](C[C@@H]7O)([H])C(C)(C)C(CC8)=O
선적

Room temperature in continental US; may vary elsewhere.
보관

Please store the product under the recommended conditions in the Certificate of Analysis.

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 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)

References

[1]. Li Y, et al. Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer. European journal of medicinal chemistry. 2024 Apr 15;270:116367. [Content Brief]

Calculators

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Mass Mass

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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.

Bioz

Keywords

MOQ

Minimum order quantity

100 mg

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