HDAC8-IN-18
HDAC8-IN-18 is an orally active HDAC8/PI3Kα inhibitor (IC50 = 0.84 µM for HDAC8; IC50 = 109.32 µM for PI3Kα). HDAC8-IN-18 targets HDAC8-mediated deacetylation of histone and non-histone lysine residues and PI3K/Akt lipid signaling, and inhibits the checkpoint kinase CHEK2, thereby inducing Apoptosis and exerting antiproliferative effects on cervical cancer cells. HDAC8-IN-18 inhibits tumor growth in a cervical cancer xenograft model, shows low cytotoxicity toward normal liver and kidney cell lines, and exhibits no teratogenic effects in zebrafish embryos. HDAC8-IN-18 can be used for research on cervical cancer.
For research use only. We do not sell to patients.
- CAS No.: 3057526-02-7
- Formula: C27H24ClN5O2
- Molecular Weight:485.96
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
HDAC8 0.84 μM (IC50) |
PI3Kα 109.32 μM (IC50) |
Chk2 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HeLa | IC50 |
1.42 μM
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Cytotoxicity against human HeLa cells assessed as viability reduction incubated 72 hrs by MTT assay.
Cytotoxicity against human HeLa cells assessed as viability reduction incubated 72 hrs by MTT assay.
|
acs.jmedchem.6c01456 |
| SiHa | IC50 |
14.30 μM
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Cytotoxicity against human SiHa cells assessed as viability reduction incubated 72 hrs by MTT assay.
Cytotoxicity against human SiHa cells assessed as viability reduction incubated 72 hrs by MTT assay.
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acs.jmedchem.6c01456 |
| Ca-Ski | IC50 |
1.40 μM
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Cytotoxicity against human Ca-Ski cells assessed as viability reduction incubated 72 hrs by MTT assay.
Cytotoxicity against human Ca-Ski cells assessed as viability reduction incubated 72 hrs by MTT assay.
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acs.jmedchem.6c01456 |
| HEK-293T | IC50 |
122.8 μM
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Cytotoxicity against human HEK293T cells assessed as viability reduction incubated 72 hrs by MTT assay.
Cytotoxicity against human HEK293T cells assessed as viability reduction incubated 72 hrs by MTT assay.
|
acs.jmedchem.6c01456 |
In Vitro
HDAC8-IN-18 (2 μM; 24 h) alters the expression of 162 genes in HeLa cells and enriches the PI3K-Akt signaling pathway[1].
HDAC8-IN-18 (2-8 μM; 48 h) inhibits the phosphorylation of PI3K/AKT/mTOR and HDAC8 in HeLa cells in a dose-dependent manner, while increasing Ac-SMC3[1].
HDAC8-IN-18 (6.25-100 μM) binds HDAC8 in BLI with a Kd of 4.21 × 10-6 M and binds PI3Kα with a Kd of 3.81 × 10-5 M[1].
HDAC8-IN-18 (10 μM) shows 89.2% inhibition of CHEK2 across a panel of 80 kinases[1].
HDAC8-IN-18 (4 μg/mL; 15-120 min) has a half-life of 67 min in rat plasma, with 37.20% remaining at 120 min[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HeLa cells
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Concentration:2, 4, and 8 μM
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Incubation Time:48 h
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Result:The percentage of apoptotic HeLa cells increased in a dose-dependent manner across 2, 4, and 8 μM.
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Cell Line:HeLa cells
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Concentration:2, 4, and 8 μM
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Incubation Time:48 h
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Result:Phosphorylation of PI3K, AKT, and mTOR was dose-dependently suppressed; HDAC8 expression was reduced; and Ac-SMC3 levels were increased at 8 μM.
Parmacokinetics
In Vivo
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, 6 weeks old, 18-20 g)[1]
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Dosage:15 mg/kg (i.p.); 30 mg/kg (i.p.); 60 mg/kg (i.p.); 25 mg/kg (i.g.); 50 mg/kg (i.g.); 100 mg/kg (i.g.)
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Administration:i.p.; i.g.; once daily for 14 days
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Result:Produced dose-dependent inhibition of tumor growth in the HeLa xenograft model.
Tumor growth inhibition reached 88.4% at 60 mg/kg i.p. and 57.1% at 100 mg/kg i.g. (p.o.); the i.p. route showed better efficacy than i.g.
Immunohistochemistry showed reduced p-PI3K and HDAC8 expression in tumor tissues, and TUNEL assay indicated induction of apoptosis.
- Mammalian live/dead viability and cytotoxicity staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Patient-Derived Orthotopic Xenograft (PDOX)
- Cell Viability Determination by MTT Colorimetric Assay
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Cell Cytotoxicity Assay
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 3057526-02-7
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Molecular Weight 485.96
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Formula C27H24ClN5O2
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SMILES
O=C(NO)C1=CC=C(C2=NC3=CC(N4CCN(C)CC4)=C(C#CC5=CC=CC=C5Cl)C=C3N2)C=C1
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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)
HDAC8-IN-18 Related Classifications
HY-191413 Related Classifications
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