PROTAC HDAC6 degrader 10
PROTAC HDAC6 degrader 10 is a highly efficient, safe and selective HDAC6 degrader with a pIC50 of 8.75 and a pDC50 of 9.2 in BEAS-2B cells. PROTAC HDAC6 degrader 10 recruits cereblon to form a ternary complex with HDAC6, thereby achieving the degradation of HDAC6. PROTAC HDAC6 degrader 10 significantly induces hyperacetylation of α-tubulin without affecting the acetylation of H3, and achieves sustained HDAC6 knockdown in mouse lung tissues. PROTAC HDAC6 degrader 10 exhibits high bioavailability after subcutaneous administration in mice. PROTAC HDAC6 degrader 10 enables the study of HDAC6 pharmacology via chemical knockdown of HDAC6 in vitro and in vivo, and can be used for research on pulmonary diseases.
(Pink: HDAC6 ligand (HY-184430); Blue: Cereblon ligand (HY-133144); Black: linker).
For research use only. We do not sell to patients.
- Formula: C37H34N4O8
- Molecular Weight:662.69
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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hHDAC6 9.2 (pIC50) |
PROTAC HDAC6 degrader 10 (compound 15) potently inhibits human HDAC6 enzymatic activity in a cell-free assay with a pIC50 of 8.75[1].
PROTAC HDAC6 degrader 10 induces complete, cereblon-dependent HDAC6 degradation in BEAS-2B cells with a subnanomolar pDC50 of 9.10[1].
PROTAC HDAC6 degrader 10 potently induces α-tubulin hyperacetylation in BEAS-2B cells with a pIC50 of 7.61[1].
PROTAC HDAC6 degrader 10 does not induce histone H3 hyperacetylation in BEAS-2B cells, demonstrating selective HDAC6 activity over class I HDAC isoforms[1].
PROTAC HDAC6 degrader 10 shows low cytotoxicity in THP1 cells, consistent with selective HDAC6 activity[1].
PROTAC HDAC6 degrader 10 has a favorable in vitro secondary pharmacology profile with limited off-target activity and no genotoxicity in micronucleus testing[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PROTAC HDAC6 degrader 10 (50 mg/kg; subcutaneous injection; single administration) induces 75% degradation of HDAC6 in mouse lung tissues at 96 h after a single dose[1].
An 86% degradation rate is achieved after 4 consecutive days of administration, accompanied by significant hyperacetylation of α-tubulin[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57/Bl (female)[1]
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Dosage:2 mg/kg; 10 mg/kg; 50 mg/kg
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Administration:s.c.; single dose
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Result:Caused significant, dose-dependent degradation of lung HDAC6 relative to vehicle control.
Caused significant, dose-dependent increases in lung acetylated α-tubulin levels relative to vehicle control .
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Animal Model:C57/Bl (female); HDAC6 knockout[1]
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Dosage:50 mg/kg
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Administration:s.c.; single dose
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Result:Achieved 75% HDAC6 degradation in lung tissue 96 hours post single dose.
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Animal Model:C57/Bl (female); HDAC6 knockout[1]
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Dosage:50 mg/kg
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Administration:s.c.; daily; 4 days
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Result:Achieved 86% HDAC6 degradation in lung tissue 24 hours after the final of four daily doses.
Induced robust α-tubulin hyperacetylation in lung tissue after repeated dosing, similar to levels in HDAC6 knockout mice .
Chemical Information
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Molecular Weight 662.69
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Formula C37H34N4O8
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SMILES
O=C(C1=CC=C2CN(C(C3CCOCC3)=O)[C@@H](C4=CC=C(C#CC5=CC6=C(C(N(C(CC7)C(NC7=O)=O)C6)=O)C=C5)C=C4)COC2=C1)NO
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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)
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