JH-1
JH-1 is an orally active and selective KDM1A inhibitor (IC50 = 0.035 μM). JH-1 reversibly inhibits KDM1A and blocks histone demethylation; it binds KDM1A intracellularly and elevates H3K4me1/2 methylation levels in a dose-dependent manner. JH-1 induces ferroptosis and apoptosis in esophageal cancer cells, upregulates ACSL4, BAX, and Cleaved‑caspase‑3, downregulates GPX4 and Bcl‑2, and increases ROS and MDA. JH-1 inhibits tumor growth and upregulates ferroptosis and apoptosis markers in the KYSE510 esophageal cancer xenograft model. JH-1 can be used for research related to esophageal cancer.
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- CAS. Nr.: 3128804-75-8
- Formel: C24H24N4O
- Molecular Weight:384.47
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
Caspase 3 |
Bax |
Bcl-2 |
GPX4 |
ACSL4 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| KYSE-510 | IC50 |
5.86 μM
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Cytotoxicity against human KYSE510 esophageal cancer cells assessed as viability reduction incubated 5 days by CCK-8 assay.
Cytotoxicity against human KYSE510 esophageal cancer cells assessed as viability reduction incubated 5 days by CCK-8 assay.
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acs.jmedchem.6c01218 |
| HET-1A | IC50 |
23.24 μM
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Cytotoxicity against human HET-1A normal esophageal epithelial cells assessed as viability reduction incubated 5 days by CCK-8 assay.
Cytotoxicity against human HET-1A normal esophageal epithelial cells assessed as viability reduction incubated 5 days by CCK-8 assay.
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acs.jmedchem.6c01218 |
In Vitro
JH-1 (0.5-4 μM; 5 days) inhibits KDM1A demethylase activity in KYSE510 cells, increases H3K4me1/2 without affecting H3K4me3; promotes the ferroptosis-related protein profile and activates intrinsic apoptosis markers in KYSE510 cells; the mediated changes in histone methylation depend on KDM1A[1].
JH-1 (5 days) selectively reduces KYSE510 cell viability compared with HET-1A cells, with KYSE510 IC50 = 5.86 μM and HET-1A IC50 = 23.24 μM[1].
JH-1 (0.5-4 μM; 7 days) inhibits clonogenic growth of KYSE510 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KYSE510 cells, KYSE510 KDM1A knockout cells
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Concentration:0.5, 1, 2, and 4 μM
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Incubation Time:5 days
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Result:Upregulated ACSL4 and downregulated GPX4. Upregulated cleaved-caspase3, cleaved-PARP1, Bax, and P53, and downregulated PARP1 and pro-caspase3.
Did not change KDM1A expression; H3K4me1 and H3K4me2 levels increased in a dose-dependent manner; H3K4me3 was unaffected.
Had no effect on H3K4me1, H3K4me2, or H3K4me3 methylation in KDM1A KO cells.
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Cell Line:KYSE510 cells
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Concentration:0.5, 1, 2, and 4 μM
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Incubation Time:7 days
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Result:Inhibited KYSE510 colony formation.
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Cell Line:KYSE510 cells
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Concentration:0.5, 1, 2, and 4 μM
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Incubation Time:5 days
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Result:Induced dose-dependent apoptosis in KYSE510 cells, and the induced apoptosis largely depends on KDM1A.
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Cell Line:KYSE510 cells
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Concentration:2 μM
2 μM (Fer-1); 2 μM (Z-VAD-FMK) -
Incubation Time:5 days
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Result:Reduced KYSE510 survival, and both Fer-1 and Z-VAD-FMK significantly alleviated cell death.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | T1/2 | MRT0-inf | AUC0-last | AUCinf |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 40 mg/kg | p.o. | 0.42 h | 422 ng/mL | 0.95 h | 1.65 h | 925 ng·h/mL | 930 ng·h/mL |
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-nu (female, 5-6 weeks old, 18-20 g, 1 × 107 KYSE510 cells were subcutaneously injected into the right axillary region)[1]
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Dosage:10 mg/kg/day; 20 mg/kg/day; 40 mg/kg/day
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Administration:p.o.; daily; 2 weeks
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Result:Suppressed KYSE510 xenograft tumor growth, with reduced tumor volume during the 2-week administration period and decreased tumor weight in the 10, 20, and 40 mg/kg/day groups compared with vehicle.
Promoted lipid ROS accumulation in tumor tissues in a dose-dependent manner.
Increased intratumoral ACSL4 and BAX protein expression and decreased GPX4 expression; immunohistochemistry showed increased cleaved-caspase3 in tumor tissues.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Annexin V plus membrane-impermeant dye apoptosis staining
- ROS/oxidative-stress fluorescent staining
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Patient-Derived Orthotopic Xenograft (PDOX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Ferroptosis Solutions
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS. Nr. 3128804-75-8
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Molecular Weight 384.47
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Formel C24H24N4O
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SMILES
OC(C=C1)=CC=C1C2=CC=C3C(N=CN=C3NC4=CC=C(N(CC)CC)C=C4)=C2
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
JH-1 Related Classifications
HY-190906 Related Classifications
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Keywords
- JH-1
- 3128804-75-8
- JH1
- JH 1
- Histone Demethylase
- Caspase
- Glutathione Peroxidase
- ACSL Family
- Bcl-2 Family
- Reactive Oxygen Species (ROS)
- Ferroptosis
- Apoptosis
- KDM1A
- apoptosis
- esophageal cancer
- ferroptosis
- glutathione redox imbalance
- histone H3 lysine 4 methylation
- histone demethylation
- lipid ROS
- lysine-specific demethylase 1
- p53
- Inhibitor
- inhibitor
- inhibit