PROTAC HDAC6/ERα degrader 1
PROTAC HDAC6/ERα degrader 1 is a dual-target PROTAC that targets HDAC6/ERα, with DC50 values of 1.21 μM (HDAC6), 0.28 μM (ERα) in MCF-7 cells and 0.67 μM (HDAC6), 0.14 μM (ERα) in LCC2 cells, respectively. PROTAC HDAC6/ERα degrader 1 selectively degrades ERα and HDAC6 via the proteasomal pathway, inhibits the transcriptional activation of ERα and blocks the estrogen signaling pathway. PROTAC HDAC6/ERα degrader 1 inhibits the function of HDAC6, attenuates hormone responses, and disrupts autophagy-lysosome function. PROTAC HDAC6/ERα degrader 1 induces cell cycle arrest, apoptosis and ferroptosis, and exhibits antiproliferative activity in breast cancer cells. PROTAC HDAC6/ERα degrader 1 can be used for breast cancer research.
(Pink: HDAC6 and ERα ligand (HY-187388); Blue: VHL ligand (HY-112078A); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3092711-76-4
- Formula: C64H77F3N6O12S2
- Molecular Weight:1243.45
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
HDAC6 0.67-1.21 μM (DC50) |
ERα 0.14-0.28 μM (DC50) |
In Vitro
PROTAC HDAC6/ERα degrader 1 (0.5-10 μM; 14 days) potently suppresses the colony-forming capacity of MCF-7 and Tamoxifen-resistant LCC2 breast cancer cells[1].
PROTAC HDAC6/ERα degrader 1 (50 μM; 30 min) directly binds to ERα and HDAC6 in breast cancer cell protein extracts, as demonstrated by increased thermal stability in CETSA assays[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MCF-7, LCC2
-
Concentration:0-50 μM (dose-response); 1 μM (colocalization and proteasome inhibition experiments); 5 μM (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal pretreatment)
-
Incubation Time:24 h (colocalization and proteasome inhibition experiments)
-
Result:Induced dose-dependent degradation of ERα and HDAC6 without affecting HDAC1, HDAC2, or HDAC4.
In MCF-7 cells, the DC50 was 0.28 μM for ERα and 1.21 μM for HDAC6; in LCC2 cells, the DC50 was 0.14 μM for ERα and 0.67 μM for HDAC6.
Degradation was blocked by pretreatment with the proteasome inhibitor carbobenzoxy-L-leucyl-L-leucinal.
Confirmed reduced ERα and HDAC6 levels in MCF-7 cells after treatment.
-
Cell Line:MCF-7, LCC2
-
Concentration:5-10 μM
-
Incubation Time:48 h
-
Result:Induced G1 phase arrest in both cell lines: in MCF-7 cells, G1 phase proportion increased to 86.8% (5 μM) and 84.9% (10 μM); in LCC2 cells, G1 phase proportion increased to 87.9% (5 μM) and 83.7% (10 μM).
Dose-dependently downregulated cell cycle regulatory proteins CyclinD1 and CDC2 in MCF-7 cells, and PCNA, CyclinD1, CDK2, and CDC2 in LCC2 cells.
-
Cell Line:MCF-7, LCC2
-
Concentration:10-20 μM (MCF-7 flow cytometry); 5-10 μM (LCC2 flow cytometry); 0-10 μM (Western blot)
-
Incubation Time:72 h (flow cytometry); 48 h (MCF-7 Western blot); 72 h (LCC2 Western blot)
-
Result:Dose-dependently increased apoptotic cell proportion: in MCF-7 cells, apoptotic cells reached 23.3% (10 μM) and 33.6% (20 μM); in LCC2 cells, apoptotic cells reached 30.1% (5 μM) and 27.0% (10 μM).
Dose-dependently downregulated antiapoptotic protein Bcl-2 in both cell lines, with no change in pro-apoptotic protein Bax.
In Vivo
PROTAC HDAC6/ERα degrader 1 (10 mg/kg; i.p.; every other day) potently suppresses tumor growth in Tamoxifen-resistant LCC2 breast cancer xenografts in female BALB/c nude mice, with an acceptable safety profile[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c nude (female, breast cancer MCF-7 cell xenograft model)[1]
-
Dosage:10 mg/kg
-
Administration:i.p.; every other day
-
Result:Reduced tumor volume and end-point tumor weight to levels superior to Ful and SAHA at the same dose.
Reduced the Ki67 proliferation index in tumor tissues.
Mediated potent proteasomal degradation of ERα and HDAC6 in tumor samples.
Exhibited no significant body weight fluctuations or histopathological evidence of cardiotoxicity, hepatotoxicity, or nephrotoxicity.
-
Animal Model:BALB/c nude (female, tamoxifen-resistant breast cancer LCC2 cell xenograft model)[1]
-
Dosage:10 mg/kg
-
Administration:i.p.; every other day
-
Result:Inhibited tumor growth and reduced end-point tumor weight to levels superior to Ful and SAHA at the same dose.
Significantly reduced the Ki67 proliferation index in tumor tissues.
Downregulated ERα and HDAC6 protein levels in tumor samples.
Exhibited no toxic side effects or significant body weight fluctuations.
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Protocol for Cell Cycle
- Breast Cancer Modeling
- Cell Viability Determination by MTT Colorimetric Assay
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Research Protocol for Endocrine Diseases
- Autophagy
- Apoptosis Solutions
- Lysosome and acidic-vesicle live-cell staining
- Ferroptosis Solutions
- Macroautophagy Solutions
Chemical Information
-
CAS No. 3092711-76-4
-
Molecular Weight 1243.45
-
Formula C64H77F3N6O12S2
-
SMILES
FC(F)(F)CN(C1=CC=C(C=C1)OCCCCCCC(N[C@@H](C(C)(C)C)C(N2[C@@H](C[C@H](C2)O)C(N[C@@H](C3=CC=C(C4=C(C)N=CS4)C=C3)C)=O)=O)=O)S(=O)([C@@H]5[C@@]6([H])C(C7=CC=C(C=C7)NC(CCCCCCC(O)=O)=O)=C(C8=CC=C(C=C8)O)[C@](C5)([H])O6)=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
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC HDAC6/ERα degrader 1 Related Classifications
HY-187387 Related Classifications
Powered by Bioz