AQ-101
AQ-101 is a MDM2 degrader. Upon binding to MDM2, it blocks the MDM2-MDM4 interaction, inducing autoubiquitination and proteasome-mediated degradation of MDM2. AQ-101 activates p53, upregulates downstream targets including p21 and PUMA, and induces apoptosis and cell cycle arrest in tumor cells. AQ-101 inhibits the progression of acute lymphoblastic leukemia in xenograft animal models. AQ-101 can be used for research related to acute lymphoblastic leukemia.
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- CAS No.: 1353384-61-8
- Formule: C16H10ClNO5
- Masse moléculaire:331.71
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Stockage:
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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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HeLa | IC50 |
2.21 μM
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Cytotoxicity against human cervical cancer HeLa (p53-repressed) cells assessed by MTT assay after 24 h incubation.
Cytotoxicity against human cervical cancer HeLa (p53-repressed) cells assessed by MTT assay after 24 h incubation.
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31324563 |
| T98G | IC50 |
>12.5 μM
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Cytotoxicity against human glioblastoma multiforme T98G (mutant p53) cells assessed by MTT assay after 24 h incubation.
Cytotoxicity against human glioblastoma multiforme T98G (mutant p53) cells assessed by MTT assay after 24 h incubation.
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31324563 |
| K562 | IC50 |
0.93 μM
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Cytotoxicity against human leukemia K562 (p53-null) cells assessed by MTT assay after 24 h incubation.
Cytotoxicity against human leukemia K562 (p53-null) cells assessed by MTT assay after 24 h incubation.
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31324563 |
| MOLT-4 | IC50 |
0.69 μM
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Cytotoxicity against human leukemia Molt-4 (wild-type p53) cells assessed by MTT assay after 24 h incubation.
Cytotoxicity against human leukemia Molt-4 (wild-type p53) cells assessed by MTT assay after 24 h incubation.
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31324563 |
In Vitro
AQ-101 binds non-covalently to the MDM2 RING domain with a Kd of 0.31 μM, and does not bind to the MDM4 RING domain; it also binds to MDM2 with a Kd of 0.37 μM, and does not bind to MDM4[1].
AQ-101 (0.25-2 μM; 0-24 h) induces dose-dependent downregulation of MDM2 protein, which starts at 2 h post-treatment, while upregulating p53 expression in EU-1 ALL cells. It reduces the stability of MDM2 protein and increases the stability of p53 protein in EU-1 ALL cells, and the degradation of MDM2 depends on the proteasome pathway[1].
AQ-101 (0.25-2 μM; 20-24 h) potently induces cytotoxicity in ALL cell lines (Sup-B13, EU-1, EU-3) expressing wild-type p53/MDM2, but shows reduced activity in the ALL cell line expressing mutant p53/MDM2 (EU-6) and the p53-deficient/MDM2-deficient ALL cell line (EU-8); it also exhibits only extremely low cytotoxicity against normal human NBMM cells[1].
AQ-101 (0.5-1 μM; 10 days) potently inhibits the colony-forming growth of EU-1 ALL cells, shows weak activity against EU-6 and EU-8 ALL cells, and exerts only extremely weak inhibitory effects on the colony-forming growth of normal human NBMM cells[1].
AQ-101 (24 h) induces cytotoxicity in HeLa, K562, Molt-4 and EU-1 cancer cell lines, with IC50 values ranging from 0.69 µM to 2.21 µM[2].
AQ-101 (0.5-1 μM; 24 h) potently induces apoptosis in acute lymphoblastic leukemia (ALL) cell lines (Sup-B13, EU-1, EU-3) expressing wild-type p53/MDM2, while its activity is reduced in ALL cell lines expressing mutant p53/MDM2 (EU-6) as well as those with p53 deletion/MDM2 deletion (EU-8)[1].
AQ-101 (0.5-1 μM; 8 h) induces p53-dependent G1 cell cycle arrest in wild-type p53 EU-1 acute lymphoblastic leukemia (ALL) cells, and G2-M cell cycle arrest in mutant p53 EU-6 ALL cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:EU-1 ALL cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Induced remarkable downregulation of MDM2 but not other tested protein levels.
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Cell Line:EU-1 ALL cells
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Concentration:0, 0.25, 0.5, 1, 2 μM (dose-response)
1 μM (time-course) -
Incubation Time:8 h
0, 2, 4, 8, 24 h -
Result:Showed the dose-response
(left) and time-course (right) of MDM2 and p53 expression in EU-1 cells treated by
AQ-101.
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Cell Line:EU-1 ALL cells
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Concentration:1 μM
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Incubation Time:0, 2, 4, 8 h
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Result:Demonstrated no inhibition of MDM2 mRNA expression by AQ‑101; instead, significantly elevated the MDM2 mRNA level upon AQ‑101 exposure.
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Cell Line:ALL cell lines (Sup-B13, EU-1, EU-3), mutant p53/MDM2-expressing (EU-6), p53-null/MDM2-null (EU-8) ALL cell lines, Normal human bone marrow mononuclear cells
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Concentration:0.25, 0.5, 1, 2 μM
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Incubation Time:20 h
24 h (NBMM cells) -
Result:Induced apoptosis in wild-type p53/MDM2-expressing ALL cell lines (Sup-B13, EU-1, EU-3).
Reduced activity in mutant p53/MDM2-expressing (EU-6) and p53-null/MDM2-null (EU-8) ALL cell lines.
Exhibited minimal cytotoxicity against normal human NBMM cells.
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Cell Line:ALL cell lines (Sup-B13, EU-1, EU-3)
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Concentration:0.5, 1 μM
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Incubation Time:24 h
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Result:Induced apoptosis in wild-type p53/MDM2-expressing ALL cell lines (Sup-B13, EU-1, EU-3).
Reduced activity in mutant p53/MDM2-expressing (EU-6) and p53-null/MDM2-null (EU-8) ALL cell lines.
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Cell Line:ALL cell lines (EU-1, EU-6, EU-8)
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Concentration:0.5, 1 μM
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Incubation Time:10 days
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Result:Inhibited clonogenic growth of EU-1 ALL cells, has reduced activity against EU-6 and EU-8 ALL cells.
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Cell Line:EU-1, EU-1
(+sip53) cells -
Concentration:0.5, 1 μM
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Incubation Time:8 h
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Result:Induced p53-dependent G1 cell-cycle arrest in wild-type p53 EU-1 ALL cells and G2-M cell-cycle arrest in mutant p53 EU-6 ALL cells.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (5-week-old female; human EU-1 ALL cell line engrafted via tail vein injection of 107 cells/mouse)[1]
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Dosage:10 mg/kg; 15 mg/kg; 20 mg/kg
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Administration:i.p.; 24-hour intervals for 3 days, repeated after a 4-day rest
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Result:Enabled 62.5% survival rate (5/8 mice) at 10 mg/kg up to 150 days post-inoculation.
Enabled 75% survival rate (6/8 mice) at 15 mg/kg up to 150 days post-inoculation.
Achieved 100% survival rate (8/8 mice) at 20 mg/kg up to 150 days post-inoculation.
Prevented detection of human ALL blasts in peripheral blood and human β-globin gene via PCR at 20 mg/kg.
Allowed weight gain throughout observation period across all doses.
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Animal Model:SCID mice (5-week-old female; luciferase-transfected human EU-1 ALL cell line engrafted via tail vein injection of 107 cells/mouse)[1]
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Dosage:10 mg/kg; 15 mg/kg; 20 mg/kg
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Administration:i.p.; 24-hour intervals for 3 days, repeated after a 4-day rest
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Result:Enabled 60% survival rate (3/5 mice) at 10 mg/kg up to 150 days post-inoculation.
Enabled 80% survival rate (4/5 mice) at 15 mg/kg up to 150 days post-inoculation.
Achieved 100% survival rate (5/5 mice) at 20 mg/kg up to 150 days post-inoculation.
Eliminated detectable leukemia via bioluminescence imaging at 20 mg/kg.
Allowed weight gain throughout observation period across all doses.
Chemical Information
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CAS No. 1353384-61-8
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Masse moléculaire 331.71
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Formule C16H10ClNO5
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SMILES
O=C1C=2C=CC=C(O)C2C(=O)C3=C(O)C=C(C=C13)NC(=O)CCl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AQ-101 Related Classifications
HY-119709 Related Classifications
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