APL-4098
APL-4098 is an orally active, selective, ATP-competitive GCN2 inhibitor with a Ki of 4.39 nM and a Kd of 2.9 nM. APL-4098 reduces the phosphorylation level of eIF2α and the expression level of ATF4. APL-4098 impairs mitochondrial function and exerts cytotoxic effects on primary acute myeloid leukemia cells. APL-4098 is applicable to research related to acute myeloid leukemia.
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- No. CAS: 2752441-61-3
- Fòrmula: C17H12ClFN6O3S
- Peso molecular:434.83
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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eIF2 |
APL-4098 (0.012-1 μmol/L; 4 h) dose-dependently reduces eIF2α phosphorylation and ATF4 protein expression in glutamine-deprived U2OS osteosarcoma cells[1].
APL-4098 (100 nmol/L, 300 nmol/L, 1 μmol/L) induces cell death ex vivo in primary patient-derived AML cells (cohort 2), including cytotoxic effects on the LSC-enriched CD34+/CD38- subpopulation in some samples[1].
APL-4098 (250 nmol/L; 6, 18, 24 h) reduces mitochondrial membrane potential in MOLM-16 AML cells after 6, 18, and 24 hours of treatment[1].
APL-4098 (up to 1 μmol/L; 24 h) dose-dependently inhibits mitochondrial respiration (including basal and maximal OCR) in MOLM-16 AML cells after 24 hours of treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
APL-4098 (15 mg/kg; p.o.; once daily; for 19 consecutive days) selectively eliminates the LSC-enriched CD34+/CD38− subset in patient-derived AML PDX models, while exerting minimal effects on the overall leukemia burden[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD/SCID (female, 6-8 weeks old, subcutaneous AML CDX model)[1]
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Dosage:0.5 mg/kg; 1.5 mg/kg; 5 mg/kg
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Administration:p.o.; once daily; 11 days
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Result:Achieved 46.2% TGI at 0.5 mg/kg with low unbound plasma exposure.
Showed intermediate TGI at 1.5 mg/kg with increased unbound plasma exposure.
Reached 98.3% TGI at 5 mg/kg with the highest unbound plasma exposure.
Caused no notable consistent adverse events, including no relevant effect on body weight or survival.
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Animal Model:NOG (female, 6-8 weeks old, patient-derived AML PDX model)[1]
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Dosage:15 mg/kg
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Administration:p.o.; once daily; 19 days
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Result:Exerted minimal effect on bulk leukemia (percentage of viable hCD45+ cells).
Pronounced and selectively depleted the LSC-enriched CD34+/CD38- subpopulation, significantly reducing cell numbers relative to vehicle control.
Caused no apparent cytotoxicity in experimental animals.
Chemical Information
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No. CAS 2752441-61-3
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Peso molecular 434.83
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Fòrmula C17H12ClFN6O3S
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SMILES
COC1=C(C=C(C=N1)Cl)S(=O)(NC2=NC=CC(C#CC3=CN=C(N=C3)N)=C2F)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
APL-4098 Related Classifications
HY-181959 Related Classifications
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- APL-4098
- 2752441-61-3
- APL4098
- APL 4098
- Eukaryotic Initiation Factor (eIF)
- patient-derived xenograft models
- mitochondrial function
- CD34+/CD38- subpopulation
- MOLM-16 AML cells
- GCN2
- cell line-derived xenograft models
- acute myeloid leukemia cells
- eIF2α
- ATF4
- mitochondrial oxidative phosphorylation
- Inhibitor
- inhibitor
- inhibit