apPHOTAC-I-2C
apPHOTAC-I-2C is an arylazopyrazole-based photoswitchable PROTAC and CRBN-binding degrader that binds CRBN with human IC50 values of 15.9 nM and 33.5 nM, and achieves light-controlled targeted degradation of BET proteins (BRD2, BRD3, BRD4) and MTH1 in a manner dependent on CRBN and the proteasome pathway. apPHOTAC-I-2C can be used for research on acute lymphoblastic leukemia.
For research use only. We do not sell to patients.
- Formula: C42H43ClN12O5S
- Molecular Weight:863.39
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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
IC50 & Target
[1]|
Cereblon 15.9 nM (IC50, dark) |
Cereblon 33.5 nM (IC50, irradiation) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| RS4-11 | DC50 |
1.05 μM
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Degradation of BRD4 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
Degradation of BRD4 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
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D6MD00266H |
| RS4-11 | DC50 |
164 nM
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Degradation of BRD3 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
Degradation of BRD3 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
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D6MD00266H |
| RS4-11 | DC50 |
484 nM
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Degradation of BRD2 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
Degradation of BRD2 in human RS4;11 cells upon 360 nm irradiation for 4 hrs by western blot analysis.
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D6MD00266H |
In Vitro
apPHOTAC-I-2C exhibits high isomer purity and durable thermal stability in DMSO-d6 and a DMSO:PBS (8:2) mixture[1].
After photoisomerization of apPHOTAC-I-2C to the cis state, the CRBN binding affinity decreases by approximately 2-fold, with IC50 values of 15.9 nM (dark) and 33.5 nM (irradiation)[1].
apPHOTAC-I-2C (up to 30 μM; 4 h) induces potent light-dependent degradation of BRD4, BRD3, and BRD2 in RS4;11 cells after 4 h, with DC50 values of 1.05 μM, 164 nM, and 484 nM, respectively[1].
apPHOTAC-I-2C (1 μM; 24 h) enables light-controlled ON/OFF regulation of BRD3 degradation in RS4;11 cells, with brief illumination sufficient to sustain continuous degradation[1].
apPHOTAC-I-2C (1 μM; 4 h)-mediated BRD3 degradation in RS4;11 cells is photochemically reversible and is restored upon 525 nm irradiation[1].
apPHOTAC-I-2C (1-10 μM; 24 h) induces light-dependent degradation of BRD3 in RS4;11 cells, with a 4.1-fold decrease in degradation levels after irradiation following 10 μM treatment for 24 h[1].
apPHOTAC-I-2C (1-10 μM; 24 h) induces light-dependent changes in neosubstrate levels in RS4;11 cells, with Ikaros decreasing 1.6-fold and GSPT1 increasing 1.8-fold after 24 h of irradiation at 10 μM[1].
apPHOTAC-I-6C (10-300 μM; 4 h) effectively degrades BRD3 in RS4;11 cells under both dark and 360 nm light conditions, with DC50 values of 29.8 nM and 39.7 nM, respectively[1].
Photo-dependent degradation of BRD3 by apPHOTAC-I-2C (4 h) in RS4;11 cells depends on CRBN binding, BET bromodomain binding, proteasome activity, neddylation, and lysosomal function[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:RS4;11
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Concentration:10, 30, 100, 300 nM; 1, 10, 30 μM
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Incubation Time:4 h
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Result:Showed no detectable degradation in the absence of light across all concentrations after 4 hours.
Induced robust degradation of BRD4 with a DC50 = 1.05 μM and Dmax = 67% upon 360 nm irradiation.
Induced robust degradation of BRD3 with a DC50 = 164 nM and Dmax = 90% upon 360 nm irradiation.
Induced robust degradation of BRD2 with a DC50 = 484 nM and Dmax = 81% upon 360 nm irradiation.
No hook effect was observed up to 30 μM under light.
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Cell Line:RS4;11
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Concentration:1 μM
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Incubation Time:24 h
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Result:In the absence of light, BRD3 levels remained indistinguishable from vehicle controls.
Pulsed 525 nm irradiation produced no detectable degradation.
A brief 60-second light dose was sufficient to clear BRD3 after 12 hours without further irradiation.
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Cell Line:RS4;11
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Concentration:1 μM
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Incubation Time:4 h (100 ms per 10 s), then monitored over 24 h
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Result:Under green light, BRD3 levels began to recover by 12 hours, nearing baseline levels after 24 hours.
Extended incubation without additional light input did not halt degradation, and BRD3 levels remained suppressed throughout the experiment.
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Cell Line:RS4;11
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Concentration:1, 10, 100 nM; 1, 10 μM
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Incubation Time:24 h
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Result:At 10 μM, BRD3 levels decreased 4.1-fold upon irradiation compared to dark conditions.
Some dark degradation was observed, though this was abolished at ≤ 1 μM.\nAt 10 μM, Ikaros exhibited a modest 1.6-fold reduction in abundance upon irradiation.
At 10 μM, GSPT1 levels increased 1.8-fold upon irradiation relative to dark.
Aiolos levels were not impacted across any light condition or concentration.
Chemical Information
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Molecular Weight 863.39
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Formula C42H43ClN12O5S
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SMILES
O=C1NC(CCC1N2CC(C(/N=N/C3=C(C)N(CCC(NCCNC(C[C@H]4C5=NN=C(C)N5C(SC(C)=C6C)=C6C(C7=CC=C(Cl)C=C7)=N4)=O)=O)N=C3C)=CC=C8)=C8C2=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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
apPHOTAC-I-2C Related Classifications
HY-189451 Related Classifications
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