country

Change Language

EN - English
FR - Français
DE - Deutsch
ES - Español
JA - 日本語
KO - 한국어

Country or Region:

United States

Product Name	Size / Unit Price	Qty

Total: USD 0.00 Checkout

Cat. No.: HY-180909

Copy Link Print Information

TMU454

TMU454 is an ASGPR-targeting GalNAc-PROTAC BRD4 degrader conjugate. TMU454 undergoes ASGPR-mediated endocytosis and CTSB cleavage to release MZ1, which selectively degrades BRD4 in ASGPR-positive hepatocellular carcinoma cells via the VHL/UPS/proteasome pathway. TMU454 inhibits cancer cell proliferation and colony formation, and suppresses tumor growth in vivo. TMU454 can be used for research related to hepatocellular carcinoma.
(Pink: BRD4 ligand (HY-13030); Blue: VHL ligand (HY-125845); Black: linker (HY-140189)).

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

Formula: C₁₄₂H₂₁₄ClN₂₇O₄₄S₂
Molecular Weight:3102.96

Storage:

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

Data Sheet (302 KB)

TMU454 Chemical Structure

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Use of MCE Products

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

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

TMU454 is an ASGPR-targeting GalNAc-PROTAC BRD4 degrader conjugate. TMU454 undergoes ASGPR-mediated endocytosis and CTSB cleavage to release MZ1, which selectively degrades BRD4 in ASGPR-positive hepatocellular carcinoma cells via the VHL/UPS/proteasome pathway. TMU454 inhibits cancer cell proliferation and colony formation, and suppresses tumor growth in vivo. TMU454 can be used for research related to hepatocellular carcinoma^[1]. (Pink: BRD4 ligand (HY-13030); Blue: VHL ligand (HY-125845); Black: linker (HY-140189)).

IC₅₀ & Target

^[1]

BRD4

All PROTACs Isoforms :

All Epigenetic Reader Domain Isoforms :

In Vitro

TMU454 (0.01-1 μM; 1-24 h) preferentially degrades BRD4 in ASGPR-positive hepatocellular carcinoma cells (HepG2 and Huh7), while showing limited activity in ASGPR-negative cancer cells and normal cells^[1].
TMU454 (1 μM; 12 h)-mediated BRD4 degradation depends on the ubiquitin-proteasome system in HepG2 and Huh7 cells^[1].
TMU454 (1 μM; 12 h)-induced BRD4 degradation is reversible in HepG2 and Huh7 cells^[1].
TMU454 (1 μM; 3 h) degrades BRD4 in HepG2 cells, and this activity is competitively inhibited by the tri-GalNAc ligand and attenuated by the endocytosis inhibitor MβCD, indicating that the entry of TMU454 and BRD4 degradation depend on ASGPR-mediated endocytosis^[1].
TMU454 (48 h) exhibits antiproliferative activity against Huh7 cells with an IC₅₀ of 481.9 nM^[1].
TMU454 (1 μM; 3 days) inhibits the colony formation ability of Huh7 cells^[1].
TMU454 (40 μM; 0.25-4 h) is efficiently cleaved by CTSB in vitro to release MZ1^[1].

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

Western Blot Analysis^[1]

Cell Line:

HepG2, Huh7, DU145, HeLa, and HK-2
Concentration:

0.01, 0.03, 0.1, 0.3, 1 μM (HepG2, Huh7, DU145); 0.1 μM (HepG2, DU145); 0.1, 1 μM (HeLa, HK-2)
Incubation Time:

3 h (HepG2, Huh7, DU145); 1, 3, 6, 12, 24 h (HepG2, DU145); 12 h (HeLa, HK-2)
Result:

Effectively degraded BRD4 in a concentration-dependent manner in ASGPR-positive HepG2 and Huh7 cells and in a time-dependent manner in HepG2 cells.
Exhibited no noticeable BRD4 degradation in ASGPR-negative DU145 cells.
Demonstrated substantially lower BRD4 degradation in normal HK-2 cells.

Western Blot Analysis^[1]

Cell Line:

HepG2 and Huh7
Concentration:

1 μM
Incubation Time:

12 h
Result:

Co-treatment with MG132 completely abolished BRD4 degradation induced by TMU454 in both HepG2 and Huh7 cells.

Western Blot Analysis^[1]

Cell Line:

HepG2 and Huh7
Concentration:

1 μM
Incubation Time:

12 h
Result:

Following compound removal and incubation with fresh medium for an additional 12 h, BRD4 levels in both HepG2 and Huh7 cells were restored.

Western Blot Analysis^[1]

Cell Line:

HepG2
Concentration:

1 μM
Incubation Time:

3 h
Result:

Pretreatment with tri-GalNAc-alkyne significantly impaired TMU454-induced BRD4 degradation in HepG2 cells.\nMβCD substantially reduced TMU454's efficacy in degrading BRD4 in HepG2 cells.\nPretreatment with CA-074Me completely blocked TMU454-induced BRD4 degradation in HepG2 cells.

Cell Proliferation Assay^[1]

Cell Line:

Huh7
Concentration:

1 μM
Incubation Time:

3 days
Result:

Inhibited the colony-forming ability of Huh7 cells.

In Vivo

TMU454 (10 mg/kg; i.p.; once daily; 7 days) exhibits potent antitumor activity in a Huh7-derived liver cancer xenograft model with minimal systemic toxicity^[1].

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

Animal Model:

BALB/c nude mice (female, 4 weeks old)^[1]
Dosage:

10 mg/kg
Administration:

i.p.; once daily; 7 days
Result:

Robustly suppressed tumor growth, outperforming the MZ1-treated groups, without inducing notable body weight loss.
Revealed no apparent toxicity in heart, liver, kidney, and spleen.

Related Protocols :

Chemical Information

Molecular Weight 3102.96
Formula C₁₄₂H₂₁₄ClN₂₇O₄₄S₂
SMILES

OC[C@@H](O1)[C@H](O)[C@H](O)[C@@H](NC(C)=O)[C@@H]1OCCCCC(NCCCNC(CCOCC(COCCC(NCCCNC(CCCCO[C@H]2[C@H](NC(C)=O)[C@@H](O)[C@@H](O)[C@@H](CO)O2)=O)=O)(COCCC(NCCCNC(CCCCO[C@H]3[C@H](NC(C)=O)[C@@H](O)[C@@H](O)[C@@H](CO)O3)=O)=O)NC(CCCC4=CN(N=N4)CCOCCOCCC(N[C@@H](C(C)C)C(N[C@@H](CCCNC(N)=O)C(NC(C=C5)=CC=C5COC(O[C@@H](C6)C[C@@H](C(NCC7=CC=C(C8=C(C)N=CS8)C=C7)=O)N6C([C@H](C(C)(C)C)NC(COCCOCCOCCNC(C[C@H](N=C9C(C=C%10)=CC=C%10Cl)C%11=NN=C(C)N%11C%12=C9C(C)=C(C)S%12)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (302 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]. Peng Y, et al. Development of Cathepsin B-Responsive GalNAc-PROTACs for Hepatocyte-Targeting Protein Degradation. Journal of medicinal chemistry. 2026 Jan 08;69(1):517-532. [Content Brief]

Calculators

Molarity Calculator

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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

Get Quote In-stock

Other size

Get Quote

Amount: USD 0.00

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

TMU454

All PROTACs Isoforms

All Epigenetic Reader Domain Isoforms

Biological Activity

Description

IC50 & Target

In Vitro

In Vivo

Chemical Information

Purity & Documentation

References

Calculators

Help & FAQs

TMU454 Related Classifications

HY-180909 Related Classifications

Bioz

Keywords

Your Recently Viewed Products

IC₅₀ & Target