PROTAC ATR degrader-4
PROTAC ATR degrader-4 is a PROTAC-based ATR kinase degrader, with a DC50 of 6.18 μM and a Dmax of 71.42% in LoVo cells. PROTAC ATR degrader-4 downregulates ATR protein expression, inducing nuclear envelope rupture, genomic instability, DNA damage and apoptosis. PROTAC ATR degrader-4 exhibits anti-tumor activity in xenograft tumor mouse models and can be used for the research of atm-deficient cancers.
(Pink: ATM/ATR ligand (HY-184294 ); Blue: Cereblon ligand (HY-10984); Black: linker).
For research use only. We do not sell to patients.
- Formula: C35H34N8O6
- Molecular Weight:662.69
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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
- Purity & Documentation
- References
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Biological Activity
PROTAC ATR degrader-4 (compound I-1) (100 nM) binds to ATR kinase and inhibits its activity by 60.2% at a concentration of 100 nM[1].
PROTAC ATR degrader-4 (72 h) exhibits potent antiproliferative activity in ATM-deficient cancer cells (LoVo, NCI-H23, GRANTA-519) and ATM-proficient HCT116 cells, with minimal cytotoxicity in normal NCM460 cells, achieving an IC50 of 4.5 μM in LoVo cells[1].
PROTAC ATR degrader-4 (1.56-25 μM; 48 h) selectively degrades ATR protein in LoVo and HCT116 cells, with no observable degradation of other PIKK family members, DDR-related proteins, or GSPT1 at concentrations up to 25 μM[1].
PROTAC ATR degrader-4 (6.25 μM; 48 h)-mediated ATR protein degradation in LoVo cells is dependent on ATR binding, CRBN recruitment, the ubiquitination system, and the proteasomal degradation pathway[1].
PROTAC ATR degrader-4 (1.56-25 μM; 48 h) inhibits the ATR/CHK1 signaling pathway in LoVo cells by reducing ATR protein levels and subsequent phosphorylation of ATR and CHK1, without degrading CHK1 itself[1].
PROTAC ATR degrader-4 (5-10 μM; 72 h) induces dose-dependent DNA damage in LoVo cells, with more significant effects than the ATR inhibitor ZH-25 at lower concentrations[1].
PROTAC ATR degrader-4 (5-10 μM; 48 h) induces dose-dependent apoptosis in LoVo cells, with greater activity at 5 μM than the ATR inhibitor ZH-25 at 10 μM[1].
PROTAC ATR degrader-4 (5-10 μM; 48 h) reduces the G2/M phase population in LoVo cells at 5 μM similar to the ATR inhibitor ZH-25, but has minimal cell cycle effects at 10 μM, suggesting potential kinase-independent antitumor mechanisms[1].
PROTAC ATR degrader-4 (5-25 μM; 24 h) disrupts nuclear envelope integrity in LoVo cells, leading to increased DNA damage and apoptosis markers in a concentration-dependent manner, with more potent effects than the ATR inhibitor ZH-25, indicating kinase-independent antitumor activity[1].
PROTAC ATR degrader-4 (3.13-25 μM; 48 h) exerts its effects in LoVo cells by degrading ATR protein rather than inhibiting ATR transcription[1].
PROTAC ATR degrader-4 (48 h) exhibits synergistic antiproliferative activity with the ATM inhibitor AZ32 in ATM-proficient HCT116 cells, reducing its IC50 from 15.57 μM to 7.89 μM when combined with 2 μM AZ32[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Cmax | AUC0-t | Vss | CL |
|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 2.54 h | 3944.78 ng/mL | 2267.80 | 4607 L/kg | 0.44 L/h/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 6-8 weeks old, subcutaneous xenograft model)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Inhibited LoVo xenograft tumor growth in a dose-dependent manner.
Reduced ATR protein levels in tumor tissue to ~65% of the control group at 25 mg/kg.
Reduced ATR protein levels in tumor tissue to ~25% of the control group at 50 mg/kg.
Caused no significant changes in mouse body weight during the treatment period.
Chemical Information
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Molecular Weight 662.69
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Formula C35H34N8O6
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SMILES
C[C@@H]1COCCN1C2=NC(C3=CC=CC4=C3C=CN4)=NC5=C2CCN(C5)CC(NC6=C7C(N(C(C7=CC=C6)=O)C8CCC(NC8=O)=O)=O)=O
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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)
PROTAC ATR degrader-4 Related Classifications
HY-184293 Related Classifications
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