PI3Kδ/HDAC6-IN-1
PI3Kδ/HDAC6-IN-1 (Compound 22E) is an orally active and dual inhibitor of PI3Kδ and HDAC6 with IC50 values of 2.4 nM and 6.2 nM, respectively. PI3Kδ/HDAC6-IN-1 exhibits potent antiproliferative effects on non-Hodgkin lymphoma (NHL) cells and possesses in vivo antitumor activity without significant toxicity. PI3Kδ/HDAC6-IN-1 arrests the cell cycle at the G0/G1 phase and induces apoptosis. PI3Kδ/HDAC6-IN-1 blocks the PI3K/AKT/mTOR signaling pathway and increases the acetylation levels of α-tubulin and histone H3.
For research use only. We do not sell to patients.
- CAS No.: 3075011-99-0
- Formula: C34H38N10O4
- Molecular Weight:650.73
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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
Biological Activity
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PI3Kδ 2.4 nM (IC50) |
HDAC6 6.2 nM (IC50) |
PI3Kδ/HDAC6-IN-1 (compound 22E) (0.1 nM -10 μM, 24-120 h) shows inhibitory activity against both PI3Kδ and HDAC6 with IC50 values of 2.4 nM and 6.4 nM, and exhibits antiproliferative activity against JEKO-1 cells[1].
PI3Kδ/HDAC6-IN-1 (10-30 μM, 45 °C-85 °C) improves thermal stability of PI3Kδ and HDAC6[1].
PI3Kδ/HDAC6-IN-1 (0.1-10 μM, 4 days) inhibits the proliferation of NHL cells, with IC50 values of 34 nM (SU-DHL-6 cells) and 53 nM (JEKO-1 cells)[1].
PI3Kδ/HDAC6-IN-1 (0.3-9 μM, 24 h) induces G0/G1 phase arrest in the SU-DHL-6 and JEKO-1 cells[1].
PI3Kδ/HDAC6-IN-1 (0.3-9 μM, 72 h) induces apoptosis (Annexin V positive) concentration-dependent in the SU-DHL-6 and JEKO-1 cells[1].
PI3Kδ/HDAC6-IN-1 (0.3-9 μM, 12 h) inhibits PI3K and HDAC-related proteins at the cellular level in the SU-DHL-6 and JEKO-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:SU-DHL-6 and JEKO-1 cells
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Concentration:0.3 μM, 1 μM, 3 μM, 9 μM
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Incubation Time:24 h
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Result:Increased the ratio of cells in G0/G1 phase, blocked cancer cells in the G0/G1 phase.
Downregulated cyclin D1, cyclin E1, CDK6, CDK4, and CDK2 proteins.
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Cell Line:SU-DHL-6 and JEKO-1 cells
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Concentration:0.3 μM, 1 μM, 3 μM, 9 μM
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Incubation Time:72 h
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Result:Induced Annexin V positivity, downregulated the anti-apoptotic protein BCL-2, increased levels of cleaved PARP and cleaved caspase-3.
Induced a concentration-dependent increase in the ROS-positive cell count in JEKO-1 cells.
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Cell Line:SU-DHL-6 and JEKO-1 cells
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Concentration:0.3 μM, 1 μM, 3 μM, 9 μM
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Incubation Time:12 h
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Result:Inhibited hosphorylation of downstream signaling proteins of PI3K, including AKT, P70S6K, and 4EBP1, as well as the oncogene-encoded protein c-MYC, while having no effect on total protein levels.
Increased histone H3 and α-tubulin acetylation levels.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ |
|---|---|---|---|---|---|---|---|---|---|
| Rat | 25 mg/kg | p.o. | 0.540 h | 0.139 h | 47.1 ng/mL | 14.9 ng·h/mL | 15.7 ng·h/mL | 0.494 h | 0.667 h |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SU-DHL-6 and JEKO-1 tumor xenograft models in NOD-SCID mice[1]
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Dosage:25 mg/kg
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Administration:p.o., 21 days
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Result:Reduced tumor growth, exhibited antitumor activity, with corresponding TGI rates of 69.42 % in the SU-DHL-6 model and 67.56 % in the JEKO-1 model.
Reduced p-AKT levels and increased acetyl-α-tubulin levels, reduced Ki-67 levels and increased cleaved caspase-3 levels.
Chemical Information
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CAS No. 3075011-99-0
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Molecular Weight 650.73
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Formula C34H38N10O4
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SMILES
CCC(N1C2=NC(N(C)C(CN3C(CN(CC4=CC=C(/C=C/C(NO)=O)C=C4)CC3)=O)=N5)=C5C(N6CCOCC6)=N2)=NC7=C1C=CC=C7
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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)
PI3Kδ/HDAC6-IN-1 Related Classifications
HY-174396 Related Classifications
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