Art. -Nr.: HY-176220

GPX4-AUTAC

GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader (AUTAC). GPX4-AUTAC consists of an inhibitor ML162-yne (HY-153748), a degradation tag FBnG (HY-W073762) and a glycol linker (HY-W021401). GPX4-AUTAC promotes the ubiquitination of GPX4 by E3 ligase TRAF6, and enhances the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. GPX4-AUTAC significantly induces ferroptosis and shows a potent anti-cancer activity in breast cancer cells, breast cancer-derived organoids (PDOs) and MDA-MB-231 tumor xenograft mice model, with potent synergistic effects when combined with Sulfasalazine (SAS) (HY-14655) or chemotherapy drugs (Paclitaxel (HY-B0015) or Cisplatin (HY-17394)).

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CAS. Nr.: 3060458-90-1
Formel: C₅₀H₅₅Cl₂FN₁₂O₉S₂
Molecular Weight:1122.08

Speicherung:

-20°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

GPX4-AUTAC Chemical Structure

CAS. Nr.: 3060458-90-1

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Use of MCE Products

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

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

Biologische Aktivität

Beschreibung

IC₅₀ & Target

GPX4

Alle Glutathione Peroxidase Isoform-spezifische Produkte anzeigen :

GPX1
GPX4

In Vitro

GPX4-AUTAC (5-80 μM, 12-72 h) significantly reduces the protein level of GPX4 in a dose- and time-dependent manner, but barely affects the mRNA level of GPX4 in MDA-MB-231 and MCF-7 cells ^[1].
GPX4-AUTAC (20-40 μM, 24 h) effectively reduces the protein level of GPX4 in ovarian cancer, lung cancer, melanoma, and glioma cells^[1].
GPX4-AUTAC (10 μM, 24-96 h, 37-57°C) continuously down-regulates GPX4 protein level for 96 h and significantly enhances the thermal stability of GPX4 in heat-denatured intact cells and cell lysates in MDA-MB-231 and MCF-7 cells^[1].
GPX4-AUTAC (5-80 μM, 24 h) selectively degrades GPX4 without influence other selenoproteins expression, such as of GPX1, TXNRD1 (GPX4 homologs) or HK2 (a TRAF6/p62 substrate)^[1].
GPX4-AUTAC selectively degrades GPX4 and induces ferroptosis in tumor cells (MDA-MB-231 cells) with minimal effect on normal cells (MCF-10A cells)^[1].
GPX4-AUTAC (10 μM, 24 h) autophagy-dependently accelerates GPX4 degradation, increases polyubiquitylation of GPX4, specifically the endogenous and exogenous K63-linked ubiquitin chains in HEK293T cells^[1].
GPX4-AUTAC (10-40 μM, 12 h) is reversed by PYR-41, NH4Cl and 3-MA to reduce the down-regulation of GPX4 in MDA-MB-231 cells^[1].
GPX4-AUTAC (24 h) induces co-localization of GPX4 and p62 and increases co-localization of GPX4 with LC3B or LAMP2 in PDOs^[1].
GPX4-AUTAC (40?μM, 24?h) selectively targets GPX4 and ferroptosis is significantly enriched in MDA-MB-231 cells^[1].
GPX4-AUTAC (5-40 μM, 72 h) has a specific ferroptosis inductive effect, and significantly enhanced the lipid ROS and promoted accumulation of Fe²⁺ in MDA-MB-231 cells, but only fully rescued by the ferroptosis inhibitor Ferrostatin-1 (Fer-1) (HY-100579) in MCF-7 cells^[1].
GPX4-AUTAC (5-80 μM) induces ferroptosis with mitochondrial dysfunction (abnormal morphology, dense content and disrupted crista) and significant increase in mRNA levels of PTGS2 in MDA-MB-231^[1].
GPX4-AUTAC (5-40 μM, 24-96 h) dose- and time-dependently inhibited cell viability and proliferation, with insensitivity to knock-down of GPX4 in both MDA-MB-231 and MCF-7 cells^[1].
GPX4-AUTAC (5-40 μM, 4 days) significantly inhibits the growth of PDOs with reducing diameter and bright-field, and PDOs with high expression of GPX4 increases sensitivity ^[1].
GPX4-AUTAC (10-20 μM, 4 days) down-regulates GPX4 expression and induces ferroptosis with high level of 4-HNE, and inhibits cancer cell proliferation in PDOs with low level of Ki67^[1].
GPX4-AUTAC induces much more ferroptosis and has a stronger anti-cancer effect in combination with Sulfasalazine compared to Sulfasalazine alone treatment in MDA-MB-231 and MCF-7 cells and PDOs ^[1].
GPX4-AUTAC (10?μM, 72 h or 4 days) sensitizes MDA-MB-231 and HCC1806 cells to chemotherapy and synergistically inhibits cell viability and proliferation and the growth of PDOs in combination with chemotherapy drugs (Paclitaxel or Cisplatin)^[1].

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

Cell Viability Assay^[1]

Cell Line:

MCF-7 cells
Concentration:

5, 10, 20, 40 μM
Incubation Time:

72 h after Fer-1, Z-VAD-FMK, Nec-1, Olaparib or VX765 1 h
Result:

Had a specific ferroptosis inductive effect , only fully rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1), but not by the inhibitor of apoptosis (Z-VAD-FMK), necroptosis (Nec-1), parthanatos (Olaparib), or pyroptosis (VX765) in MCF-7 cells.

Cell Viability Assay^[1]

Cell Line:

MDA-MB-231 cells, MCF-7 cells
Concentration:

MDA-MB-231 cells, MCF-7 cells (5, 10, 20, 40 μM), shNT, shGPX4 cells (10, 20, 40, 80 μM)
Incubation Time:

72 h
Result:

Dose-dependently inhibited tumor cell viability in both MDA-MB-231, MCF-7 and shGPX4 cells.

Cell Proliferation Assay^[1]

Cell Line:

MDA-MB-231 cells, MCF-7 cells
Concentration:

5, 10 μM
Incubation Time:

24, 48, 72, 96 h
Result:

Dose- and time-dependently inhibited tumor cell proliferation in both MDA-MB-231 and MCF-7 cells.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 cells, MCF-7 cells, MCF-10A cells
Concentration:

MDA-MB-231 cells, MCF-7 cells, MCF-10A cells (5, 10, 20, 40, 80 μM)
Incubation Time:

12, 24, 48, 72 h
Result:

Significantly reduced the expression of GPX4 protein in a dose- and time-dependent manner.
Significantly reduced the expression of GPX4 in MDA-MB-231 cells with minimal effect on MCF-10A cells at 24 h.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 cells, MCF-7 cells
Concentration:

10 μM
Incubation Time:

24, 48, 72, 96 h
Result:

Continuously down-regulated GPX4 protein level for 96 h after wash-out in MDA-MB-231 and MCF-7 cells.
Significantly enhanced the thermal stability of GPX4 in heat-denatured intact cells and cell lysates in MDA-MB-231 and MCF-7 cells at 37-57℃ and 24 h.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 cells, HEK293T cells
Concentration:

10, 40 μM
Incubation Time:

12 h
Result:

Significantly accelerated the turnover rate of GPX4 in MDA-MB-231 cells when added CHX at 10 μM.
Down-regulated GPX4 expression, but this effect reversed by PYR-41 (an inhibitor of cell-permeable ubiquitin E1 enzyme) in MDA-MB-231 cells at 10 μM.
Enhanced the down-regulation of GPX4 promoted by overexpression of p62, but rescued by knockdown of p62 in HEK293T cells at 40 μM.

Real Time qPCR^[1]

Cell Line:

MDA-MB-231 cells, MCF-7 cells
Concentration:

5, 10, 20, 40, 80 μM
Incubation Time:

24 h
Result:

Played a regulatory role at the post-translational level ,and barely affected the mRNA level of GPX4 in both MDA-MB-231 and MCF-7 cells.

Immunofluorescence^[1]

Cell Line:

MDA-MB-231 cells
Concentration:

5, 10, 20, 40 μM
Incubation Time:

72 h
Result:

Significantly enhanced the lipid ROS and promoted accumulation of Fe<>sup2+ in MDA-MB-231 cells.

In Vivo

GPX4-AUTAC (10-20 mg/kg, i.p., daily for 10-12 days) has a potent anti-cancer activity, and significantly reduces tumor weights and volumes, GPX4 protein levels, and percentage of Ki67 while increasing 4-HNE levels with no significant toxicity in vital organs, through preferentially accumulation and selectively degradation of GPX4 in tumor tissues of MDA-MB-231 tumor xenograft mice model (minimal effect on normal tissues)^[1].
GPX4-AUTAC (10-20mg/kg combined Sulfasalazine 100?mg/kg, i.p., daily for 10-12 days) synergizes with Sulfasalazine to exert strong tumor suppressive activity via inducing ferroptosis with no measurable toxicity in MDA-MB-231 tumor xenograft mice model^[1].

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

Animal Model:

Female BALB/c nude mice (4-6 weeks old) were injected subcutaneously into the right flank with MDA-MB-231 cells (5 × 10⁶ cells/mouse) ^[1].
Dosage:

10, 20mg/kg
Administration:

i.p., daily for 10-12 days when the tumor size reached 50-100 mm
Result:

Selectively degraded GPX4 in tumors tissues, but not in the normal tissues including the heart, lung, liver, spleen, and kidney.
Significantly decreased tumor weights and volumes in MDA-MB-231 tumor xenograft mice model.
Markedly decreased the protein level of GPX4 in MDA-MB-231 tumor xenograft mice model.
Effectively decreased percentage of Ki67, but increased percentage of Ki67 4-HNE in MDA-MB-231 tumor xenograft mice model.

Animal Model:

Female BALB/c nude mice (4-6 weeks old) were injected subcutaneously into the right flank with MDA-MB-231 cells (5 × 10⁶ cells/mouse) ^[1].
Dosage:

10, 20mg/kg or Sulfasalazine 100 mg/kg
Administration:

i.p., daily for 10-12 days when the tumor size reached 50-100 mm
Result:

Had a synergistic inhibitory effect on tumor growth combined with SAS in MDA-MB-231 tumor xenograft mice model.
Significantly decreased expressions of GPX4 and Ki67 and increased expression of 4-HNE combined with SAS in MDA-MB-231 tumor xenograft mice model.

Related Protocols :

Chemical Information

CAS. Nr. 3060458-90-1
Appearance Solid
Molecular Weight 1122.08
Formel C₅₀H₅₅Cl₂FN₁₂O₉S₂
Color White to off-white
SMILES

O=C(C(N(C1=CC(Cl)=C(OCC(N=N2)=CN2CCOCCOCCOCCNC([C@H](CSC3=NC4=C(N3CC5=CC=C(C=C5)F)N=C(NC4=O)N)NC(C)=O)=O)C=C1)C(CCl)=O)C6=CC=CS6)NCCC7=CC=CC=C7
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-20°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (89.12 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

0.8912 mL

4.4560 mL

8.9120 mL

5 mM

0.1782 mL

0.8912 mL

1.7824 mL

10 mM

0.0891 mL

0.4456 mL

0.8912 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 (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.

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 (2.23 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 (2.23 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 (289 KB)
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)
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]. Gong R, et al. GPX4-AUTAC induces ferroptosis in breast cancer by promoting the selective autophagic degradation of GPX4 mediated by TRAF6-p62. Cell Death Differ. 2025 May 20. [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

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	0.8912 mL	4.4560 mL	8.9120 mL	22.2801 mL
	5 mM	0.1782 mL	0.8912 mL	1.7824 mL	4.4560 mL
	10 mM	0.0891 mL	0.4456 mL	0.8912 mL	2.2280 mL
	15 mM	0.0594 mL	0.2971 mL	0.5941 mL	1.4853 mL
	20 mM	0.0446 mL	0.2228 mL	0.4456 mL	1.1140 mL
	25 mM	0.0356 mL	0.1782 mL	0.3565 mL	0.8912 mL
	30 mM	0.0297 mL	0.1485 mL	0.2971 mL	0.7427 mL
	40 mM	0.0223 mL	0.1114 mL	0.2228 mL	0.5570 mL
	50 mM	0.0178 mL	0.0891 mL	0.1782 mL	0.4456 mL
	60 mM	0.0149 mL	0.0743 mL	0.1485 mL	0.3713 mL
	80 mM	0.0111 mL	0.0557 mL	0.1114 mL	0.2785 mL

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GPX4-AUTAC

Alle Glutathione Peroxidase Isoform-spezifische Produkte anzeigen