APL-4098
Based on 1 Customer Validation
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.
For research use only. We do not sell to patients.
- Purity : 99.84%
- CAS No.: 2752441-61-3
- Formula: C17H12ClFN6O3S
- Molecular Weight:434.83
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
eIF2 |
In Vitro
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. Further protocols information, click here.
Parmacokinetics
In Vivo
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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CAS No. 2752441-61-3
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Appearance Solid
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Molecular Weight 434.83
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Formula C17H12ClFN6O3S
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Color White to off-white
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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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (229.97 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (5.75 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
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Data Sheet (275 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.2997 mL | 11.4987 mL | 22.9975 mL | 57.4937 mL |
| 5 mM | 0.4599 mL | 2.2997 mL | 4.5995 mL | 11.4987 mL | |
| 10 mM | 0.2300 mL | 1.1499 mL | 2.2997 mL | 5.7494 mL | |
| 15 mM | 0.1533 mL | 0.7666 mL | 1.5332 mL | 3.8329 mL | |
| 20 mM | 0.1150 mL | 0.5749 mL | 1.1499 mL | 2.8747 mL | |
| 25 mM | 0.0920 mL | 0.4599 mL | 0.9199 mL | 2.2997 mL | |
| 30 mM | 0.0767 mL | 0.3833 mL | 0.7666 mL | 1.9165 mL | |
| 40 mM | 0.0575 mL | 0.2875 mL | 0.5749 mL | 1.4373 mL | |
| 50 mM | 0.0460 mL | 0.2300 mL | 0.4599 mL | 1.1499 mL | |
| 60 mM | 0.0383 mL | 0.1916 mL | 0.3833 mL | 0.9582 mL | |
| 80 mM | 0.0287 mL | 0.1437 mL | 0.2875 mL | 0.7187 mL | |
| 100 mM | 0.0230 mL | 0.1150 mL | 0.2300 mL | 0.5749 mL |
APL-4098 Related Classifications
HY-181959 Related Classifications
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Keywords
- 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