ZNL-02-096
ZNL-02-096 is a selective Wee1 PROTAC degrader. ZNL-02-096 binds to CRBN and Wee1 to form a ternary complex, inducing CRBN- and proteasome-dependent ubiquitination and proteasomal degradation of Wee1. ZNL-02-096 inhibits recombinant PLK1 with an IC50 of 102 nM, but does not induce its degradation in cells. ZNL-02-096 induces G2/M phase arrest, Apoptosis, transient integrated stress response, upregulation of ATF4, and phosphorylation of GCN2. ZNL-02-096 reduces Tyr15 phosphorylation of CDK1. ZNL-02-096 can be used in research related to ovarian cancer, acute lymphoblastic leukemia, triple-negative breast cancer, multiple myeloma, and pancreatic ductal adenocarcinoma.
(Pink: Wee1 ligand (HY-10993); Blue: Cereblon ligand (HY-W1005059); Black: linker).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- CAS. Nr.: 2414418-56-5
- Formel: C43H47N11O6
- Molecular Weight:813.90
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Speicherung:
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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Biologische Aktivität
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Chemical Information
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
Cereblon |
PLK1 102 nM (IC50) |
ATF4 |
GCN2 |
CDK1 |
In Vitro
ZNL-02-096 potently inhibits recombinant PLK1 protein with an IC50 value of 102 nM[1].
ZNL-02-096 (50 nM-1 μM) exhibits weaker activity than AZD1775 (HY-10993) in inducing autophosphorylation of recombinant GCN2 in vitro[2].
ZNL-02-096 (0.001-10 μM; 0.25-5 h) induces rapid, sustained, proteasome- and CRBN-dependent degradation of Wee1 in parental MOLT4 cells, and reduces the level of pCDK1 Y15[1].
ZNL-02-096 (72 h) exerts CRBN-dependent antiproliferative activity against MOLT4 cells, with an IC50 of 390 nM in parental cells and an IC50 of 2220 nM in CRBN-/- cells[1].
ZNL-02-096 activates the integrated stress response in RPE1 TP53KO cells, which is characterized by upregulated ATF4 expression and increased phosphorylation level of GCN2[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:parental MOLT4 acute lymphoblastic leukemia cells
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Concentration:0.001-10 μM (direct 5 h treatment); 100 nM (time-course treatment); 100 nM (with pre-treatment of 0.4 μM carfilzomib, 1 μM MLN4924, 10 μM pomalidomide, or 1 μM AZD1775)
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Incubation Time:5 h (0.001-10 μM treatment); 0.25-5 h, 24 h, 48 h (100 nM time-course); 2 h pre-incubation, 5 h co-treatment (pre-treatment conditions)
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Result:Induced maximal Wee1 degradation at 100 nM after 5 h.
Achieved over 50% Wee1 degradation within 30 min, complete degradation by 3 h, and sustained loss for at least 48 h.
Had its induced Wee1 degradation rescued by pre-treatment of carfilzomib, MLN4924, pomalidomide, or AZD1775.
Decreased phosphorylation of CDK1 at Tyr15 (pCDK1 Y15) starting at 100 nM after 5 h.
- Kinase activity and phosphorylation assays
- Western Blot
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Apoptosis Solutions
- Protocol for Cell Cycle
- Protocol for Kinase activity and phosphorylation assays
- Breast Cancer Modeling
Chemical Information
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CAS. Nr. 2414418-56-5
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Molecular Weight 813.90
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Formel C43H47N11O6
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SMILES
C=CCN1C(C2=C(N1C3=NC(C(C)(O)C)=CC=C3)N=C(NC4=CC=C(N5CCN(CC5)CCCNC(C=CC=C6C(N7C8CCC(N(C8=O)C)=O)=O)=C6C7=O)C=C4)N=C2)=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Li Z, et al. Development and Characterization of a Wee1 Kinase Degrader. Cell chemical biology. 2020 Jan 16;27(1):57-65.e9. [Content Brief]
[2]. Wilson JCJ, et al. WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2. Nature communications. 2025 Oct 09;16(1):8983. [Content Brief]
[3]. Liu J, et al. Cell cycle on the crossroad of tumorigenesis and cancer therapy. Trends in cell biology. 2022 Jan;32(1):30-44. [Content Brief]
[4]. Tjeerdsma RB, et al. WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response. Nature communications. 2025 Nov 24;16(1):11598. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
ZNL-02-096 Related Classifications
HY-208742 Related Classifications
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