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
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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]
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Biological Activity
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Chemical Information
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- References
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Biological Activity
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HDAC6 0.67-1.21 μM (DC50) |
ERα 0.14-0.28 μM (DC50) |
PROTAC HDAC6/ERα degrader 1 (V-12c) potently inhibits proliferation of ER+ and Tamoxifen (HY-13757A)-resistant breast cancer cell lines (MCF-7, LCC2, T47D, T47D ERαD538G, T47D ERαY537S) with IC50 values ranging from 0.23 μM to 1.23 μM, and shows low cytotoxicity in normal MCF-10A breast epithelial cells (IC50 >100 μM)[1].
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 (0-50 μM; 24 h) selectively induces proteasome-dependent degradation of ERα and HDAC6 in MCF-7 and LCC2 breast cancer cells, with DC50 values ranging from 0.14 μM to 1.21 μM[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].
PROTAC HDAC6/ERα degrader 1 (1-10 μM; 48-72 h) induces G1 phase cell cycle arrest in MCF-7 and Tamoxifen-resistant LCC2 breast cancer cells, accompanied by downregulation of key cell cycle regulatory proteins[1].
PROTAC HDAC6/ERα degrader 1 (5-20 μM; 72 h) induces apoptosis in MCF-7 and tamoxifen-resistant LCC2 breast cancer cells, with apoptotic proportions reaching 23.3−33.6% in MCF-7 (10−20 μM) and 27.0−30.1% in LCC2 (5−10 μM), accompanied by downregulation of the antiapoptotic protein Bcl-2[1].
PROTAC HDAC6/ERα degrader 1 (5 μM; 24-72 h) induces ROS-dependent ferroptosis in Tamoxifen-resistant LCC2 breast cancer cells, characterized by lipid peroxidation measured via MDA levels after 24 h, activation of the Nrf2-HMOX-1 pathway, and cytotoxicity that is partially reversed by ferroptosis and antioxidant inhibitors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7, LCC2
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Concentration:0-50 μM (dose-response); 1 μM (colocalization and proteasome inhibition experiments); 5 μM (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal pretreatment)
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Incubation Time:24 h (colocalization and proteasome inhibition experiments)
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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.
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Cell Line:MCF-7, LCC2
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Concentration:5-10 μM
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Incubation Time:48 h
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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.
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Cell Line:MCF-7, LCC2
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Concentration:10-20 μM (MCF-7 flow cytometry); 5-10 μM (LCC2 flow cytometry); 0-10 μM (Western blot)
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Incubation Time:72 h (flow cytometry); 48 h (MCF-7 Western blot); 72 h (LCC2 Western blot)
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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.
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.
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Animal Model:BALB/c nude (female, breast cancer MCF-7 cell xenograft model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; every other day
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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.
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Animal Model:BALB/c nude (female, tamoxifen-resistant breast cancer LCC2 cell xenograft model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; every other day
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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.
Chemical Information
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CAS No. 3092711-76-4
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Molecular Weight 1243.45
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Formula C64H77F3N6O12S2
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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
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Shipping
Room temperature in continental US; may vary elsewhere.
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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
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