KAT2A degrader-2
Based on 1 Customer Validation
KAT2A degrader-2 is a selective molecular glue degrader targeting KAT2A, with a DC50 of 22 nM in Kelly cells. KAT2A degrader-2 acts as a molecular glue to recruit KAT2A to CRBN, forming a ternary complex that drives the polyubiquitination and proteasome-dependent degradation of KAT2A. KAT2A degrader-2 reduces the acetylation level of histone H3 lysine 9 via the ubiquitin-like and proteasome-dependent pathway. KAT2A degrader-2 can be used for the research of acute myeloid leukemia.
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- Pureté : 96.05%
- Formule: C31H36N8O5
- Masse moléculaire:600.67
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Stockage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
KAT2A 22 nM (DC50) |
In Vitro
KAT2A degrader-2 (6 h) potently degrades endogenous KAT2A in Kelly cells with a DC50 of 22 nM and 90% maximum degradation after 6-hour treatment[1].
KAT2A degrader-2 (0.1-1 μM; 6 h) selectively degrades KAT2A over KAT2B, GSPT1, and GSPT2 in Kelly cells, functionally reducing H3K9Ac levels in a CRBN- and proteasome-dependent manner after 6-hour treatment[1].
KAT2A degrader-2 (1 μM; 6 h) exhibits exquisite proteome-wide selectivity, degrading only KAT2A in Kelly cells after 6-hour treatment with 1 μM[1].
KAT2A degrader-2 selectively recruits KAT2A to CRBN in Kelly cell lysates, with no other off-target proteins showing significant enrichment[1].
KAT2A degrader-2 (0.1-1 μM; 6 h) functionally inhibits KAT2A activity, reducing H3K9Ac levels in a CRBN- and proteasome-dependent manner in EOL-1 and MV4;11 AML cells after 6-hour treatment[1].
KAT2A degrader-2 (1 μM; 6 h) maintains exquisite proteome-wide selectivity, degrading only KAT2A in EOL-1 and MV4;11 AML cells after 6-hour treatment with 1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Kelly neuroblastoma cells
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Concentration:0.1-1 μM; 0.25 μM (combined with 1 μM MLN4924 or bortezomib)
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Incubation Time:6 h; 6 h (after MLN4924 or bortezomib pretreatment)
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Result:Induced dose-dependent degradation of KAT2A, with negligible degradation of the homologous KAT2B at doses >250 nM, and no degradation of GSPT1 or GSPT2 up to 1 μM.
Caused dose-dependent reduction of histone H3 lysine 9 acetylation (H3K9Ac), a primary KAT2A substrate.
Had its induced KAT2A degradation and H3K9Ac reduction blocked by pretreatment with the neddylation inhibitor MLN4924 or proteasome inhibitor bortezomib.
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Cell Line:MV4;11 (KMT2A::AFF1), EOL-1 (KMT2A partial tandem duplication), MOLM13 (KMT2A::MLLT3), MONOMAC6 (KMT2A::MLLT3), NB-4 (PML::RARA), NOMO1 (KMT2A::MLLT3), THP-1 (KMT2A::MLLT3)
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Concentration:10-10-10-5 M
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Incubation Time:9 days (with retreatment as needed)
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Result:Induced antiproliferative activity with IC50 = 32.7 nM in MV4;11 cells, IC50 = 40.6 nM in EOL-1 cells, IC50 = 37.3 nM in MOLM13 cells, and IC50 = 70.1 nM in MONOMAC6 cells.
Caused minimal sensitivity in NB-4, NOMO1, and THP-1 cells, with IC50 values >10,000 nM.
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Cell Line:EOL-1 and MV4;11 AML cell lines
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Concentration:0.1-1 μM; 0.25 μM (combined with 1 μM MLN4924 or bortezomib)
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Incubation Time:6 h; 6 h (after MLN4924 or bortezomib pretreatment)
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Result:Induced dose-dependent reduction of H3K9Ac in both EOL-1 and MV4;11 cells.
Had its induced H3K9Ac reduction blocked by pretreatment with MLN4924 or bortezomib, confirming dependence on neddylation and proteasome function.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunodeficient mice[1]
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Dosage:20 mg/kg
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Administration:s.c.; daily; 27 days
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Result:Improved median survival to 47.5 days.
Decreased human CD45+ leukemia burden in peripheral blood at days 26, 34, and 41.
Induced potent KAT2A degradation in harvested human CD45+ cells.
Reduced global H3K9Ac levels in harvested human CD45+ cells.
Caused no treatment-related changes in body weight or circulating blood cell counts.
Chemical Information
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Appearance Solid
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Masse moléculaire 600.67
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Formule C31H36N8O5
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Color White to off-white
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SMILES
O=C(N1)CCC(N2CC(C(NC3=C(N=CN4C5OCCCC5)C4=CC(N6CCN(C(C)(C)C)C6=O)=N3)=CC=C7)=C7C2=O)C1=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvant et solubilité
In Vitro:
DMSO : 50 mg/mL (83.24 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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 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.
Working solution concentration: 0.22 mg/mL
Pureté et documentation
Références
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 (sealed storage, away from moisture). 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 | 1.6648 mL | 8.3240 mL | 16.6481 mL | 41.6202 mL |
| 5 mM | 0.3330 mL | 1.6648 mL | 3.3296 mL | 8.3240 mL | |
| 10 mM | 0.1665 mL | 0.8324 mL | 1.6648 mL | 4.1620 mL | |
| 15 mM | 0.1110 mL | 0.5549 mL | 1.1099 mL | 2.7747 mL | |
| 20 mM | 0.0832 mL | 0.4162 mL | 0.8324 mL | 2.0810 mL | |
| 25 mM | 0.0666 mL | 0.3330 mL | 0.6659 mL | 1.6648 mL | |
| 30 mM | 0.0555 mL | 0.2775 mL | 0.5549 mL | 1.3873 mL | |
| 40 mM | 0.0416 mL | 0.2081 mL | 0.4162 mL | 1.0405 mL | |
| 50 mM | 0.0333 mL | 0.1665 mL | 0.3330 mL | 0.8324 mL | |
| 60 mM | 0.0277 mL | 0.1387 mL | 0.2775 mL | 0.6937 mL | |
| 80 mM | 0.0208 mL | 0.1041 mL | 0.2081 mL | 0.5203 mL |
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