PROTAC HDAC3 degrader-1
PROTAC HDAC3 degrader-1 is a selective PROTAC degrader targeting HDAC3 with a DC50 of 30.73 nM. PROTAC HDAC3 degrader-1 induces degradation of HDAC3 via the ubiquitin-proteasome system. PROTAC HDAC3 degrader-1 promotes apoptosis, induces DNA damage, and downregulates anti-apoptotic proteins Mcl-1 and Bcl-xL. PROTAC HDAC3 degrader-1 can be used for the research of acute myeloid leukemia.
(Pink: HDAC3 ligand (HY-181768); Blue: VHL ligand (HY-125845); Black: linker).
For research use only. We do not sell to patients.
- Formula: C50H63N9O7S
- Molecular Weight:934.16
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
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HDAC3 30.73 nM (DC50) |
Bcl-xL |
Mcl-1 |
PROTAC HDAC3 degrader-1 (b22) (20 nM, 200 nM; 12 h) induces HDAC3 degradation in MV4-11 cells, with 24.4% degradation at 20 nM and 81.8% degradation[1].
PROTAC HDAC3 degrader-1 induces HDAC3 degradation in THP-1 AML cells with a DC50 of 143.1 nM[1].
PROTAC HDAC3 degrader-1 (0.5-1000 nM; 24 h) induces concentration-dependent HDAC3 degradation in MV4-11 cells, with a DC50 of 30.73 nM and a maximum degradation efficiency of 82% after 24 h of treatment[1].
PROTAC HDAC3 degrader-1 (200 nM; 0.5-24 h) induces time-dependent HDAC3 degradation in MV4-11 cells, reaching maximum levels within 8 h and sustaining degradation[1].
PROTAC HDAC3 degrader-1 (8-1000 nM; 12 h) exhibits highly selective degradation of HDAC3 over other HDAC isoforms (HDAC1, HDAC2, HDAC4, HDAC6, HDAC11) in MV4-11 cells at concentrations up to 200 nM, with an effect on HDAC8 only seen at ≥1000 nM after 12 h of treatment[1].
PROTAC HDAC3 degrader-1 (48 h) exhibits moderate antiproliferative activity against MV4-11 AML cells with an IC50 of 1.26 μM after 48 h of treatment, and significantly reduced cytotoxicity against Kasumi-1, THP-1, HL-7702, and iBMDMs cells[1].
PROTAC HDAC3 degrader-1 (0.078-2.500 μM; 48 h) synergizes with Venetoclax (HY-15531) to inhibit MV4-11 cell proliferation, with CI values <1 for all tested concentration combinations after 48 h of treatment[1].
PROTAC HDAC3 degrader-1 (300-600 nM; 48 h) synergizes with Venetoclax to promote apoptosis in MV4-11 cells, with apoptosis rates reaching up to 88.90% after 48 h of combined treatment[1].
PROTAC HDAC3 degrader-1 (150-600 nM; 24 h) synergizes with Venetoclax in MV4-11 cells to downregulate anti-apoptotic proteins Mcl-1 and Bcl-xL, enhance DNA damage (increased γH2A.X), and activate caspase3 cleavage after 24 h of combined treatment, while b22 alone has no significant effect on these proteins[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 acute myeloid leukemia (AML) cells
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Concentration:20 nM; 200 nM
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Incubation Time:12 h
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Result:Induced 24.4% HDAC3 degradation at 20 nM.
Induced 81.8% HDAC3 degradation at 200 nM.
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Cell Line:MV4-11 cells
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Concentration:0.5, 1.4, 4.1, 12.3, 37.0, 111.1, 333.3, 1000 nM
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Incubation Time:24 h
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Result:Induced concentration-dependent HDAC3 degradation with a DC50 of 30.73 nM and a maximum degradation efficiency (Dmax) of 82%.
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Cell Line:MV4-11 cells
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Concentration:200 nM
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Incubation Time:0.5, 1, 1, 2, 3, 4, 6, 8, 10, 12, 24 h
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Result:Reached maximum HDAC3 degradation within 8 h of treatment.
Sustained degradation levels were maintained for at least 24 h.
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Cell Line:MV4-11 cells
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Concentration:8, 40, 200, 1000 nM
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Incubation Time:12 h
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Result:Promoted efficient, dose-dependent degradation of HDAC3 specifically.
Showed no significant effects on HDAC1, HDAC2, HDAC4, HDAC6, or HDAC11 at concentrations up to 200 nM.
Caused a significant effect on HDAC8 only at concentrations ≥ 1000 nM.
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Cell Line:MV4-11 cells
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Concentration:2.500, 1.250, 0.625, 0.313, 0.156, 0.078 μM (PROTAC HDAC3 degrader-1); 0.031, 0.063, 0.125 μM (Venetoclax)
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Incubation Time:48 h
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Result:Produced combination index (CI) values < 1 for all tested combinations with Venetoclax, indicating synergistic antiproliferative effects.
CI values ranged from 0.066 to 0.611 across the tested concentration combinations.
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Cell Line:MV4-11 cells
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Concentration:300, 600 nM (PROTAC HDAC3 degrader-1 alone); 300, 600 nM (PROTAC HDAC3 degrader-1) + 30, 60 nM (Venetoclax) (HY-15531) (combined)
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Incubation Time:48 h
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Result:Induced 11.40% apoptosis at 300 nM when used alone.
Induced 14.16% apoptosis at 600 nM when used alone.
Increased apoptosis rate to 63.10% when combined with 30 nM Venetoclax at 300 nM b22.
Increased apoptosis rate to 79.10% when combined with 30 nM Venetoclax at 600 nM.
Increased apoptosis rate to 69.50% when combined with 60 nM Venetoclax at 300 nM.
Increased apoptosis rate to 88.90% when combined with 60 nM Venetoclax at 600 nM.
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Cell Line:MV4-11 cells
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Concentration:150, 300, 600 nM (PROTAC HDAC3 degrader-1 alone); 150, 300, 600 nM (PROTAC HDAC3 degrader-1) + 30, 60 nM (Venetoclax) (combined)
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Incubation Time:24 h
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Result:Did not significantly alter Mcl-1 or Bcl-xL protein levels when used alone.
Dose-dependently downregulated Mcl-1 and Bcl-xL when combined with Venetoclax.
Increased γH2A.X levels (a marker of DNA double-strand breaks) when combined with Venetoclax.
Reduced pro-caspase3 levels when combined with Venetoclax.
Synergistically increased cleaved caspase3 levels when combined with Venetoclax.
| Species | Dose | Route | Cmax | AUC0-inf | T1/2 | Vss | CL |
|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 1454.29 ng/mL | 807.25 ng·h/mL | 1.81 h | 4.27 L/kg | 45.64 mL/min/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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Molecular Weight 934.16
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Formula C50H63N9O7S
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SMILES
O=C([C@H]1N(C([C@@H](NC(CN2CCN(CCN(CC3=CC=C(C(NNCCC)=O)C=C3)C(C4=CC5=CC=CC=C5O4)=O)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC6=CC=C(C7=C(C)N=CS7)C=C6
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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)