ZZ7-23-022
ZZ7-23-022 (ZZ7) is a selective BRD9 molecule glue degrader. ZZ7-23-022 promotes the selective degradation of BRD9 through the ubiquitin-proteasome pathway, induces BRD9-DCAF16 interaction, and forms a ternary complex by covalently binding to the Cys178 site of DCAF16. ZZ7-23-022 induces the selective degradation of BRD9 in synovial sarcoma cells but does not affect human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, while exerting antiproliferative effects on synovial sarcoma cells. ZZ7-23-022 can be used for research related to synovial sarcoma.
For research use only. We do not sell to patients.
- Formula: C36H45N7O5
- Molecular Weight:655.79
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Storage:
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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Biological Activity
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Chemical Information
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- Purity & Documentation
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Help & FAQs
Biological Activity
Description
IC50 & Target
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BRD9 |
In Vitro
ZZ7-23-022 (0.1 μM; 5 h) selectively degrades BRD9 with minimal off-target effects in MOLT-4 cells[1].
ZZ7-23-022 (0.05-3 μM; 5 h) potently degrades BRD9 in CME-1, HS-SY-II, and 1273/99 synovial sarcoma cells but has minimal effect on BRD9 in hiPSC-CMs, leveraging differential DCAF16 expression[1].
ZZ7-23-022 (2-9 days) potently inhibits the proliferation of HS-SY-II and 1273/99 synovial sarcoma cells with IC50 values of 322 nM and 426 nM, respectively[1].
ZZ7-23-022 (0.000001-100 μM; 1 h) does not impair contractile function, disrupt calcium handling, or induce arrhythmic effects in hiPSC-CMs, demonstrating a favorable cardiac safety profile[1].
ZZ7-23-022 mediates ternary complex formation between BRD9 and DCAF16 via covalent binding to DCAF16 Cys178, with a distinct BRD9 orientation relative to DCAF16 compared to BRD4-based complexes, as confirmed by cryo-EM structural analysis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat cells
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Concentration:0.01-3 μM (5 h incubation); 3 μM (0.5-5 h incubation); 1 μM (5 h incubation, preceded by 1 h pretreatment with 1 μM MLN-4924, 1 μM proteasome inhibitor, 10 μM warhead fragment, or 10 μM BI-7273)
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Incubation Time:0.5-5 h (3 μM); 5 h (0.01-1 μM, with or without 1 h pretreatment)
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Result:Induced dose-dependent degradation of BRD9, with degradation starting as early as 1 h post-treatment.
Completely rescued BRD9 degradation when cells were pretreated with MLN-4924 or proteasome inhibitor.
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Cell Line:wild-type, DCAF11-knockout, and DCAF16-knockout Jurkat cells; HEK293T cells expressing FLAG-tagged BRD9 and HA-tagged DCAF16 (wild-type or mutants); cells expressing HaloTag-DCAF16 and nanoluciferase-BRD9 fusion proteins; wild-type, DCAF16-knockout, and DCAF16-mutant K-562 cells
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Concentration:0-1 μM (5 h incubation, Jurkat knockout cells); 0-5 μM (3 h incubation, HEK293T cells); 10-10000 nM (2 h incubation, NanoBRET assay); 5 μM (3 h incubation, HEK293T cells with DCAF16 mutants); 3 μM (K-562 cells)
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Incubation Time:2 h (NanoBRET assay); 3 h (HEK293T cells, K-562 cells); 5 h (Jurkat knockout cells)
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Result:Completely abolished BRD9 degradation in DCAF16-knockout Jurkat cells but maintained degradation in DCAF11-knockout cells.
Induced dose-dependent co-immunoprecipitation of FLAG-BRD9 and HA-DCAF16 in HEK293T cells.
Enhanced the NanoBRET signal between HaloTag-DCAF16 and nanoluciferase-BRD9.
Abolished ZZ7-induced BRD9-DCAF16 interaction and BRD9 degradation when DCAF16 Cys178 was mutated, while mutation of Cys58 had no effect; mutations of Ala53, Cys177, and Cys179 also inhibited these effects.
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Cell Line:synovial sarcoma cell lines (CME-1, HS-SY-II, 1273/99), human iPSC-derived cardiomyocytes (hiPSC-CMs)
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Concentration:0.05-0.5 μM (5 h incubation, CME-1 cells); 0.1-3 μM (5 h incubation, hiPSC-CMs)
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Incubation Time:5 h
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Result:Induced robust BRD9 degradation in CME-1, HS-SY-II, and 1273/99 synovial sarcoma cell lines, at levels comparable to CRBN-based BRD9 PROTACs.
Had minimal effect on BRD9 levels in hiPSC-CMs.
Chemical Information
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Molecular Weight 655.79
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Formula C36H45N7O5
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SMILES
CC(N1CCN(C2COC2)CC1)(C)/C=C(C(N3CCN(CC4=C(OC)C=C(C(C5=CC=NC=C65)=CN(C)C6=O)C=C4OC)CC3)=O)\C#N
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Synonyms
ZZ7
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZZ7-23-022 Related Classifications
HY-178345 Related Classifications
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