MS83
MS83 is a selective degrader of BRD4/BRD3 belonging to the PROTAC class. MS83 hijacks the KEAP1-dependent CUL3 ligase complex by binding to KEAP1 and forming a ternary complex with BRD4/BRD3. MS83 induces polyubiquitination and degradation of BRD4/BRD3 in a concentration-, time- and ubiquitin-proteasome system-dependent manner. MS83 inhibits c-MYC protein levels and suppresses the proliferation of triple-negative breast cancer cells.
(Pink: BRD4 ligand (HY-78695); Blue: Keap1-Nrf2 ligand (HY-145390); Black: linker).
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- CAS No.: 2762181-19-9
- Formule: C52H55ClN10O8S2
- Masse moléculaire:1047.64
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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BRD4 |
BRD3 |
In MDA-MB-468 cells, MS83 (25 nM-10 μM; 12-72 h) durably degrades BRD4 (L/S) and BRD3 (but not BRD2) in a concentration-dependent manner, reaching 80% maximum BRD4 degradation at 0.5 μM after 48 h, and reduces c-MYC protein levels at 0.25 μM and above[1].
In MDA-MB-231 cells, MS83 (25 nM-10 μM; 48 h) selectively degrades BRD4 short isoform and BRD3 (but not BRD4 long isoform or BRD2) in a concentration-dependent manner, and reduces c-MYC protein levels at 0.25 μM and above[1].
MS83 (0.5 μM; 18-24 h)-induced BRD4 degradation in MDA-MB-468 cells is dependent on the ubiquitin-proteasome system and KEAP1 recruitment, as confirmed by competition assays, KEAP1 knockdown, and induced KEAP1-BRD4 complex formation[1].
In MDA-MB-468 cells, MS83 (0.5 μM; 48 h) is highly selective for degrading BRD4 and BRD3, with minimal off-target protein downregulation in unbiased global proteomic profiling[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-468 triple-negative breast cancer cells
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Concentration:0.5 μM; 1 μM; 5 μM; 25 nM, 100 nM, 0.25 μM, 2.5 μM, 10 μM
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Incubation Time:12 h, 24 h, 36 h, 48 h, 72 h; 0, 12, 24, 36 h (cycloheximide chase)
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Result:Induced durable degradation of both BRD4 long (L) and short (S) isoforms, with effects persisting for 72 h.
Detected degradation of BRD4 (L/S) at 100 nM after 48 h.
Reached 80% maximum degradation of BRD4 at 0.5 μM.
Showed a hook effect on BRD4 degradation starting at 2.5 μM.
Induced 50% degradation of BRD3 at 0.25 μM and 0.5 μM.
Showed a hook effect on BRD3 degradation starting at 1 μM.
Did not degrade BRD2 at any concentration tested.
Confirmed clear degradation of BRD4 (S) at 24 and 36 h via cycloheximide chase experiments.
Reduced c-MYC protein levels in a concentration-dependent manner at 0.25 μM and above.
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Cell Line:MDA-MB-231 triple-negative breast cancer cells
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Concentration:25 nM, 100 nM, 0.25 μM, 0.5 μM, 1 μM, 2.5 μM, 10 μM
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Incubation Time:48 h
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Result:Potently degraded BRD4 (S) and BRD3 without an obvious hook effect.
Did not degrade BRD4 (L) or BRD2 even at 10 μM.
Reduced c-MYC protein levels in a concentration-dependent manner at 0.25 μM and above.
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Cell Line:MDA-MB-468 and MDA-MB-231 triple-negative breast cancer cells
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Concentration:Serial 3-fold dilutions
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Incubation Time:3 days
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Result:Exhibited potent antiproliferative activity in a concentration-dependent manner.
Achieved GI50 value of 280 nM in MDA-MB-468 cells.
Achieved GI50 value of 130 nM in MDA-MB-231 cells.
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Cell Line:MDA-MB-468 and MDA-MB-231 triple-negative breast cancer cells
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Concentration:Diluted concentrations
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Incubation Time:8 days
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Result:Showed a much more potent inhibitory effect on colony formation than negative control MS83N1 and CRBN-recruiting PROTAC dBET1 in both cell lines.
Chemical Information
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CAS No. 2762181-19-9
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Masse moléculaire 1047.64
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Formule C52H55ClN10O8S2
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SMILES
O=S1(C2=CC=CC=C2O[C@H](C)CN1CC3=CC([C@@H](C4=CC(OCCNC(CNC(C[C@H]5C6=NN=C(C)N6C7=C(C(C)=C(C)S7)C(C8=CC=C(Cl)C=C8)=N5)=O)=O)=C(N(C)N=N9)C9=C4)CC(OCC)=O)=CC=C3C)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS83 Related Classifications
HY-139620 Related Classifications
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