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)).
For research use only. We do not sell to patients.
- Formula: C66H53ClN14O6SZn
- Molecular Weight:1271.12
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
(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. Further protocols information, click here.
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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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Molecular Weight 1271.12
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Formula 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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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.
Protocols
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Ferroptosis Solutions
Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death characterized by lethal lipid peroxidation and sensitivity to suppression by iron chelators or lipophilic radical-trapping antioxidants. The core pathway links cystine uptake through system Xc−, glutathione availability, GPX4-dependent detoxification of phospholipid hydroperoxides, iron-dependent oxidative reactions, and polyunsaturated-phospholipid metabolism into a cell-death program that is biochemically and morphologically distinct from apoptosis, necrosis, and autophagy. The ferroptosis pathway is experimentally linked to phenotype through chemical and genetic perturbation. Erastin induces ferroptosis by inhibiting cystine uptake through system Xc− and weakening antioxidant defenses, while GPX4 inhibition or depletion causes lipid peroxide accumulation and ferroptotic cancer-cell death. ACSL4 and oxidizable arachidonoyl- or adrenoyl-containing phosphatidylethanolamines shape ferroptosis sensitivity by con
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZnPc-O3-JQ1 Related Classifications
HY-176724 Related Classifications
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