PROTAC HDAC6 degrader 7
PROTAC HDAC6 degrader 7 is an orally active, highly efficient, and selective PROTAC degrader targeting histone deacetylase 6 (HDAC6) (IC50 = 118 nM). PROTAC HDAC6 degrader 7 can eliminate both the catalytic and zinc-finger ubiquitin-binding domain. PROTAC HDAC6 degrader 7 inhibits NLRP3 inflammasome assembly and activation, as well as blocks NF-κB signaling, thereby reducing the transcription and release of key inflammatory factors. PROTAC HDAC6 degrader 7 can reduce the mRNA levels of NLRP3, pro-IL-1β, TNF-α, and IL-6. PROTAC HDAC6 degrader 7 can be used for the study of inflammatory bowel disease (IBD).
(Pink: HDAC6 ligand (HY-179422); Blue: Cereblon ligand (HY-W087383); Black: linker).
For research use only. We do not sell to patients.
- Formula: C49H54N8O6
- Molecular Weight:851.00
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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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Biological Activity
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HDAC6 118 nM (IC50) |
NF-κB |
IL-6 |
NLRP3 |
Cereblon |
PROTAC HDAC6 degrader 7 (Compound 22f) (0-2 μM, 12 h) exhibits potent HDAC6 degradation activity in MV4-11 cells in a concentration-dependent manner (DC50 = 13.4 nM)[1].
PROTAC HDAC6 degrader 7 (25-200 nM, 12 h) shows only slight degradation of IKZF1 at 200 nM, but no degradation of GSPT1 in MV4-11 cells[1].
PROTAC HDAC6 degrader 7 (0-2 μM) demonstrates high specificity toward HDAC6 (IC50 of 118 nM) and exhibits no appreciable inhibition against other HDAC isotypes at 10 μM[1].
PROTAC HDAC6 degrader 7 (0.5 μM, 0-24 h) induces HDAC6 degradation in MV4-11 cells, which was initiated within 3 hours and reached equilibrium within 12 hours, and this degradation could be rescued by CRBN ligands and proteasome inhibitors, indicating that the mechanism of action is the induction of HDAC6 degradation via the CRBN-mediated ubiquitin-proteasome pathway[1].
PROTAC HDAC6 degrader 7 (0-6 μM, 0-24 h) degrades HDAC6 in J774A.1 cells in a time-dependent manner, with a concentration-dependent DC50 of 9.20 nM[1].
PROTAC HDAC6 degrader 7 (1.4-1000 nM, 8 h) significantly inhibits IL-1β in LPS (HY-D1056)/ATP-stimulated J774A.1 cells in a concentration-dependent manner[1].
PROTAC HDAC6 degrader 7 (40-200 nM, 8 h) significantly reduces the levels of mature IL-1β and p20 in J774A.1 cells at low concentrations, and downregulates the expression of intracellular NLRP3 and pro-IL-1β proteins at high concentrations[1].
PROTAC HDAC6 degrader 7 (0.2-1 μM) dose-dependently reduces the mRNA levels of NLRP3, pro-IL-1β, TNF-α, and IL-6 in LPS-induced J774A.1 cells[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 cells
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Concentration:25 nM, 50 nM, 100 nM, 200 nM
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Incubation Time:12 h
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Result:Only IKZF1 was slightly degraded at 200 nM, but GSPT1 was not degraded.
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Cell Line:J774A.1 cells were pretreated 3 h followed by a 4.5 h pretreatment with LPS (1 μg/mL). Afterward, the cells were stimulated with ATP (5 mM) for 30 min
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Concentration:1.4 nM, 4.1 nM, 12.3 nM, 37 nM, 111 nM, 333 nM, 1000 nM
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Incubation Time:8 h
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Result:Significantly inhibited IL-1β in LPS/ATP-stimulated J774A.1 cells in a concentration-dependent manner.
| Species | Dose | Route | Cmax | T1/2 | AUC0-inf | F | Vss | CL |
|---|---|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | i.p. | 305.51 ng/mL | 1.72 h | 1397.59 ng·h/mL | 24.05 | / | / |
| Mice | 10 mg/kg | p.o. | 403.33 ng/mL | 6.26 h | 5490.11 ng·h/mL | / | / | / |
| Mice | 5 mg/kg | i.v. | 1859.4 ng/mL | 3.13 h | 2757.93 ng·h/mL | / | 4142.2 mL/kg | 26.3 mL/min/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6J mice (6-8 weeks old) were given an aqueous solution containing 2.5% (w/v) dextran sulfate sodium (DSS) for 9 days[1].
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Dosage:2 mg/kg, 10 mg/kg
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Administration:P.o., once daily for 9 days
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Result:The rate of weight loss was reduced.
Disease Activity Index (DAI) scores were significantly lowered.
The colon length in mice was significantly restored, approaching normal levels.
Mutual epithelial regeneration was promoted, inflammatory cell infiltration was reduced, and histopathological scores were significantly lowered.
The level of the inflammatory cytokine IL-1β was significantly lower than in the DSS model group, while the level of acetylated tubulin (Ac-tubulin), a specific substrate of HDAC6, was significantly upregulated.
Chemical Information
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Molecular Weight 851.00
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Formula C49H54N8O6
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SMILES
O=C(C1=CC=C(CN2C3=CC=CC=C3C=CC4=C2C=CC=C4OCCN5CCN(CC5)CC6CCN(C7=CC=C8C(C(N(C8=O)C9CCC(NC9=O)=O)=O)=C7)CC6)C=C1)NNCC
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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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