ZnPc-O3-JQ1
ZnPc-O3-JQ1 is a photoactivatable BRD4-targeting degrader and photosensitizer, composed of monosubstituted amino zinc phthalocyanine (ZnPc), the BRD4 ligand JQ1, and a PEG linker. Upon activation by light, ZnPc-O3-JQ1 generates reactive oxygen species (ROS) and induces BRD4 degradation in an E3 ubiquitin ligase-independent manner. BRD4 degradation further reduces HIF-1α and GCL levels and restricts the SLC7A11/GSH-related antioxidant response, thereby enhancing photodynamic therapy-associated oxidative stress. ZnPc-O3-JQ1 can be used in research related to bladder cancer.
(Pink: BRD4 ligand (HY-78695); Blue: Reactive Oxygen Species (ROS) and Photosensitizer ligand (HY-176725); Black: linker (HY-W040165)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C66H53ClN14O6SZn
- Peso molecular:1271.12
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Almacenamiento:
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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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
(Pink: BRD4 ligand (HY-78695); Blue: Reactive Oxygen Species (ROS) and Photosensitizer ligand (HY-176725); Black: linker (HY-W040165)).
IC50 & Target
[1]|
BRD4 22 nM (IC50) |
In Vitro
ZnPc-O3-JQ1 (compound 5c) (9 h; 680 nm light irradiation for 10 min; subsequent incubation for 15 h) reduces the viability of T24 cells, with an IC50 of 22 nM under light irradiation conditions[1].
ZnPc-O3-JQ1 (dark condition; 9 h) does not exhibit obvious dark toxicity against T24 and SV-HUC-1 cells, and the dark-condition IC50 for T24 cells is >2 × 105 nM[1].
ZnPc-O3-JQ1 (1 μM; 9 h; 10 min light irradiation) generates higher total intracellular ROS in T24 cells than ZnPc-JQ1; the two compounds produce similar levels of •OH, but ZnPc-O3-JQ1 generates more 1O2, and no O2•− is detected intracellularly[1].
ZnPc-O3-JQ1 (30 nM) exerts comparable cytotoxicity under 18% O2 and 1% O2 conditions, with activity superior to that of ZnPc-JQ1; it effectively kills T24 cells at this low concentration[1].
ZnPc-O3-JQ1 (30 nM; dark condition; 24 h) does not induce significant BRD4 degradation in T24 cells[1].
ZnPc-O3-JQ1 (30 nM; 9 h; 10 min of light irradiation; followed by 15 min of incubation) induces 87% degradation of BRD4 in T24 cells; in comparison, 10 μM dBET1 achieves a BRD4 degradation rate of 35%[1].
ZnPc-O3-JQ1 reduces the thermal stability of BRD4 in CETSA, which supports the target engagement between ZnPc-O3-JQ1 and BRD4[1].
The cellular uptake efficiency of ZnPc-O3-JQ1 in T24 cells is similar to that of ZnPc-JQ1, but it is predominantly and widely distributed in the cytoplasm and exhibits a low degree of colocalization with lysosomes[1].
ZnPc-O3-JQ1 (1 μM; 1% O2; 10 min light irradiation) reduces intracellular oxygen levels in T24 cells; ZnPc-O3-JQ1 (30 nM; 1% O2; 9 h; 10 min light irradiation; followed by 15 min incubation) decreases HIF-1α protein levels[1].
ZnPc-O3-JQ1 (30 nM; 18% O2; 9 h; 10 min of light irradiation; followed by 15 min of incubation) increases SLC7A11 protein level to 7.31-fold that of the control group and decreases GCL protein level; meanwhile, intracellular GSH level only increases to 1.37-fold that of the control group[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:T24 cell
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Concentration:30 nM
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Incubation Time:18% or 1% O2; light irradiation
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Result:Produced similar cytotoxic effects under 18% and 1% O2.
Showed stronger cytotoxicity than ZnPc-JQ1 under both oxygen conditions.
Effectively killed T24 cells at 30 nM while cisplatin and dBET1 showed negligible activity.
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Cell Line:T24 cell
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Concentration:30 nM
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Incubation Time:24 h; without light irradiation
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Result:Did not induce evident BRD4 degradation.
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Cell Line:T24 cell
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Concentration:30 nM
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Incubation Time:9 h; light irradiation for 10 min; 15 min
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Result:Degraded BRD4 by 87%.
Produced substantially greater BRD4 degradation than dBET1 at 10 μM, which degraded BRD4 by 35%.
ZnPc-JQ1 at 30 nM or 1 μM did not induce significant BRD4 degradation after light irradiation.
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Cell Line:T24 cell
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Concentration:30 nM
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Incubation Time:1% O2; 9 h; light irradiation for 10 min; 15 min
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Result:Decreased HIF-1α protein levels compared with the control and ZnPc-JQ1 groups.
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Cell Line:T24 cell
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Concentration:30 nM
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Incubation Time:18% O2; 9 h; light irradiation for 10 min; 15 min
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Result:Increased SLC7A11 protein to 7.31-fold of control.
Decreased GCL protein levels.
In Vivo
ZnPc-O3-JQ1 (3 mg/kg; administered via tail vein injection; once every 2 days for 10 days; the tumor site receives 665 nm laser irradiation at 25 mW/cm2 for 5 min daily) exerts the strongest tumor growth inhibition, induces the most prominent tumor tissue damage, and achieves nearly complete BRD4 degradation in the MB49 subcutaneous tumor-bearing model in C57BL/6 mice, without causing significant body weight loss[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice (female, 6-7 weeks old, weighing 20−22 g)[1]
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Dosage:3 mg/kg
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Administration:i.v.; once every other day; 10 days (with daily 665 nm laser irradiation 25 mW/cm2 of the tumor site for 5 min)
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Result:Achieve near-complete in vivo degradation of tumor BRD4 protein.
Show the most pronounced tumor tissue damage as observed via H&E staining.
Produce the most effective tumor growth suppression among all treatment groups.
Cause no significant changes in mouse body weight over the treatment period.
Chemical Information
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Peso molecular 1271.12
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Fòrmula C66H53ClN14O6SZn
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SMILES
O=C(NC1=CC=C(C=C1)OC2=CC3=C(C4=NC5=[N-]6C(C7=C5C=CC=C7)=NC8=C9C=CC=CC9=C%10N=C%11C%12=C(C%13=[N-]%11[Zn+2](N8%10)6N4C3=N%13)C=CC=C%12)C=C2)CCOCCOCCOCCNC(C[C@@H]%14N=C(C%15=CC=C(Cl)C=C%15)C(C(C)=C(C)S%16)=C%16N%17C%14=NN=C%17C)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZnPc-O3-JQ1 Related Classifications
HY-176724 Related Classifications
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