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).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- CAS No.: 2762181-19-9
- 화학식: C52H55ClN10O8S2
- 분자량:1047.64
-
보관:
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]
-
Biological Activity
-
Chemical Information
- 순도&문서
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
|
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.
-
Cell Line:MDA-MB-468 triple-negative breast cancer cells
-
Concentration:0.5 μM; 1 μM; 5 μM; 25 nM, 100 nM, 0.25 μM, 2.5 μM, 10 μM
-
Incubation Time:12 h, 24 h, 36 h, 48 h, 72 h; 0, 12, 24, 36 h (cycloheximide chase)
-
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.
-
Cell Line:MDA-MB-231 triple-negative breast cancer cells
-
Concentration:25 nM, 100 nM, 0.25 μM, 0.5 μM, 1 μM, 2.5 μM, 10 μM
-
Incubation Time:48 h
-
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.
-
Cell Line:MDA-MB-468 and MDA-MB-231 triple-negative breast cancer cells
-
Concentration:Serial 3-fold dilutions
-
Incubation Time:3 days
-
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.
-
Cell Line:MDA-MB-468 and MDA-MB-231 triple-negative breast cancer cells
-
Concentration:Diluted concentrations
-
Incubation Time:8 days
-
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
-
CAS No. 2762181-19-9
-
분자량 1047.64
-
화학식 C52H55ClN10O8S2
-
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
-
선적
Room temperature in continental US; may vary elsewhere.
-
보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS83 Related Classifications
HY-139620 Related Classifications
Powered by Bioz