AD-5584
Based on 1 Customer Validation
AD-5584 is a selective and blood-brain barrier-penetrant ACSS2 inhibitor (IC50 = 0.86 μM). AD-5584 binds to the nucleotide-binding pocket of ACSS2, blocking CoA binding and acetyl transfer through steric hindrance, thereby inhibiting the conversion of acetate to acetyl-CoA. AD-5584 decreases acetyl-CoA levels, lipid droplet content, FASN expression, E2F1, SLC7A11, and GPX4 levels, and reduces E2F1 occupancy at the SLC7A11 promoter. AD-5584 induces ferroptosis, lipid peroxidation, malondialdehyde accumulation, and cell death, and decreases clonogenic survival and proliferative capacity. AD-5584 can be used for research on breast cancer brain metastasis.
For research use only. We do not sell to patients.
- Purity : 99.86%
- CAS No.: 2306525-79-9
- Formula: C22H24ClFN4O
- Molecular Weight:414.90
-
Storage:Powder -20°C, 3 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]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
ACSS2 0.86 μM (IC50) |
GPX4 |
In Vitro
AD-5584 binds selectively to human ACSS2 with low-micromolar affinity and shows no binding to hACSS1[1].
AD-5584 (100 μM; 48 h) significantly reduces clonogenic survival of MDA-MB-231BR breast cancer brain metastatic cells[1].
AD-5584 induces cell death in MDA-MB-231BR and 4T1BR breast cancer brain metastatic cells[1].
AD-5584 (100 μM; 48 h) significantly reduces acetyl-CoA levels in MDA-MB-231BR and 4T1BR breast cancer brain metastatic cells[1].
AD-5584 (100 μM; 48 h) significantly reduces lipid droplet content in MDA-MB-231BR breast cancer brain metastatic cells[1].
AD-5584 (100 μM; 24 h) reduces FASN protein levels in MDA-MB-231BR breast cancer brain metastatic cells[1].
AD-5584 has a metabolic half-life of 20 min in human liver microsomes, demonstrating moderate metabolic stability[1].
AD-5584 exhibits moderate permeability in the MDR1-MDCK blood-brain barrier assay[1].
AD-5584 (100 μM; 48 h) reduces E2F1, SLC7A11, and GPX4 protein levels in MDA-MB-231-BR cells[2].
AD-5584 (100 μM; 48 h) induces ferroptotic cell death in MDA-MB-231-BR cells, which is blocked by ferrostatin-1[2].
AD-5584 (100 μM; 48 h) induces lipid peroxidation in MDA-MB-231-BR cells, which is blocked by ferrostatin-1[2].
AD-5584 (100 μM; 48 h) E2F1 overexpression protects MDA-MB-231-BR cells from AD-5584-induced cell death and lipid peroxidation[2].
AD-5584 (100 μM; 48 h) reduces E2F1, SLC7A11, and GPX4 protein levels in 4T1-BR cells[2].
AD-5584 (100 μM; 48 h) induces ferroptotic cell death in 4T1-BR cells, which is blocked by Ferrostatin-1 (HY-100579) [2].
AD-5584 (100 μM; 48 h) induces lipid peroxidation in 4T1-BR cells, which is blocked by Ferrostatin-1 (HY-100579)[2].
AD-5584 induces ferroptosis-mediated tumor regression of MDA-MB-231-BR cells in ex vivo brain slices, with no observable toxicity to normal brain tissue[2].
AD-5584 induces ferroptosis-mediated tumor regression of 4T1-BR cells in ex vivo brain slices[2].
In MDA-MB-231-BR cells, AD-5584 (50 μM; 6 hours) reduces E2F1 occupancy at the SLC7A11 promoter[3].
AD-5584 (50 μM; 6 days) significantly reduces the growth of HCI-015 patient-derived TNBC brain metastasis organoids[3].
AD-5584 (24 hours) reduces proliferation equally in both MDA-MB-231 parental and MDA-MB-231-BR cells[3].
AD-5584 increases malondialdehyde levels, a marker of lipid peroxidation and ferroptosis, in breast cancer brain metastatic cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MDA-MB-231BR breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:48 h (treatment); 15 min (staining)
-
Result:Significantly reduced lipid droplet content compared to control.
-
Cell Line:MDA-MB-231BR breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:24 h
-
Result:Reduced protein levels of FASN compared to DMSO control.
-
Cell Line:MDA-MB-231-BR human breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:48 h
-
Result:Reduced E2F1, SLC7A11, and GPX4 protein levels compared to control-treated cells.
-
Cell Line:MDA-MB-231-BR human breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:48 h
-
Result:Significantly increased cell death compared to control-treated cells.
Reversed the increase in cell death by co-treatment with Ferrostatin-1.
-
Cell Line:4T1-BR mouse breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:48 h
-
Result:Reduced E2F1, SLC7A11, and GPX4 protein levels compared to control-treated cells.
-
Cell Line:4T1-BR mouse breast cancer brain metastatic cells
-
Concentration:100 μM
-
Incubation Time:48 h
-
Result:Significantly increased cell death compared to control-treated cells.
Reversed the increase in cell death by co-treatment with Ferrostatin-1.
In Vivo
AD-5584 (systemic; 14 days) inhibits breast cancer brain metastasis growth in immunocompromised mice bearing intracranial MDA-MB-231-BR tumors[2].
AD-5584 (50 mg/kg; i.p.; daily; 10 days) suppresses breast cancer brain metastatic growth and extends survival in mouse intracranial models[3].
AD-5584 (50-100 mg/kg; i.p.; single dose) penetrates the blood-brain barrier in healthy mice in vivo[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Nu/Nu athymic nude mice (4-6 weeks old; female for MFP model) injected with f MDA-
MB-231 or MDA-MB-231-BR cells[3] -
Dosage:50 mg/kg
-
Administration:i.p.; daily; 10 days
-
Result:Significantly blocked breast cancer brain metastatic growth of both 4T1-BR and MDA-MB-231-BR cells in vivo.
Significantly extended survival of treated mice compared to control.
No weight loss or observable behavioral changes were detected in treated animals.
Chemical Information
-
CAS No. 2306525-79-9
-
Appearance Solid
-
Molecular Weight 414.90
-
Formula C22H24ClFN4O
-
Color White to off-white
-
SMILES
FC1=CC=C(C(N2CCCCC2)C(N(C)CC3=NC4=CC(Cl)=CC=C4N3)=O)C=C1
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 12.5 mg/mL (30.13 mM; ultrasonic and warming and heat to 60°C; 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)
Purity & Documentation
-
Data Sheet (286 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4102 mL | 12.0511 mL | 24.1022 mL | 60.2555 mL |
| 5 mM | 0.4820 mL | 2.4102 mL | 4.8204 mL | 12.0511 mL | |
| 10 mM | 0.2410 mL | 1.2051 mL | 2.4102 mL | 6.0255 mL | |
| 15 mM | 0.1607 mL | 0.8034 mL | 1.6068 mL | 4.0170 mL | |
| 20 mM | 0.1205 mL | 0.6026 mL | 1.2051 mL | 3.0128 mL | |
| 25 mM | 0.0964 mL | 0.4820 mL | 0.9641 mL | 2.4102 mL | |
| 30 mM | 0.0803 mL | 0.4017 mL | 0.8034 mL | 2.0085 mL |
AD-5584 Related Classifications
HY-161116 Related Classifications
Powered by Bioz