MS479
MS479 is a PROTAC degrader targeting BRD4, BRD3 and BRD2. MS479 recruits the E3 ligase SPOP by bridging the protein GLP, thereby promoting polyubiquitination modification and subsequent 26S proteasomal degradation. MS479 inhibits the proliferation of colorectal cancer cells and can be used for research on colorectal cancer and triple-negative breast cancer.
(Pink: BRD4 ligand (HY-78695); Blue: SPOP ligand (HY-176036); Black: linker (HY-176037)).
For research use only. We do not sell to patients.
- Formula: C59H82ClN11O5S
- Molecular Weight:1092.87
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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
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- References
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Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HT-29 | DC50 |
6.2 μM
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Degradation of BRD4 short isoform (BRD4 (S)) in human HT29 colorectal cancer cells assessed via Western blot-based protein degradation assay incubated for 24 hrs.
Degradation of BRD4 short isoform (BRD4 (S)) in human HT29 colorectal cancer cells assessed via Western blot-based protein degradation assay incubated for 24 hrs.
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40202531 |
| HT-29 | GI50 |
4.5 μM
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Antiproliferative activity against human HT29 colorectal cancer cells assessed as reduction in cell viability incubated for 72 hrs by WST-8 assay.
Antiproliferative activity against human HT29 colorectal cancer cells assessed as reduction in cell viability incubated for 72 hrs by WST-8 assay.
|
40202531 |
In Vitro
MS479 binds with high affinity to purified recombinant BRD4-BD2 (KD=200 nM) and GLP-SET domain (KD=306 nM)[1].
MS479 (0.156-10 μM; 2-72 h) induces concentration- and time-dependent degradation of BRD4 (S), weak degradation of BRD4 (L), BRD3, and BRD2, and potent suppression of c-MYC in HT29 cells, with BRD4 (S) degradation dependent on BRD4, GLP, and the ubiquitin-proteasome system[1].
MS479 (1-10 μM; 24 h) regulates BRD4, BRD3, and BRD2 protein levels via a post-translational mechanism and downregulates c-MYC transcription in HT29 cells[1].
MS479 (0.1-5 μM; 24 h) degrades BRD4 (S), BRD3, BRD2, and BRD4 (L) in MDA-MB-231 cells, with greater activity against BRD4 (L) than in HT29 cells[1].
MS479 (0.021-10 μM; 72 h) potently inhibits proliferation of HT29 colorectal cancer cells (GI50=4.5 μM) without affecting viability of normal PNT2 prostatic epithelial cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HT29 colorectal cancer cells
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Concentration:0.156-10 μM (24 h); 5 μM (2 h, 4 h, 8 h, 16 h, 48 h, 72 h); 1 μM (pretreatment with MS1262, JQ1, MLN4924)
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Incubation Time:2 h (pretreatment); 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h (MS479 treatment)
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Result:Induced >50% degradation of BRD4 short isoform (BRD4 (S)) at 5 μM for 24 h.
Induced degradation of BRD4 (S) with a DC50 of 6.2 μM and maximum degradation (D_max) of 63% in concentration-dependent testing.
Induced ~50% degradation of BRD4 long isoform (BRD4 (L)), weak degradation of BRD3 and BRD2, and complete suppression of c-MYC at 10 μM for 24 h.
Induced BRD4 (S) degradation detectable at 16 h and persisting to 72 h in time-dependent testing.
Required 48 h or longer for effective degradation of BRD4 (L), BRD3, and BRD2 in time-dependent testing.
Caused c-MYC levels to drop sharply starting at 2 h in time-dependent testing.
Degradation of BRD4 (S) was rescued by pretreatment with MS1262, JQ1, or MLN4924.
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Cell Line:HT29 colorectal cancer cells
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Concentration:1-10 μM
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Incubation Time:24 h
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Result:Did not alter mRNA levels of BRD4 (S), BRD4 (L), BRD3, or BRD2.
Significantly downregulated c-MYC mRNA at 5 μM and 10 μM.
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Cell Line:MDA-MB-231 triple-negative breast cancer cells
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Concentration:0.1-5 μM
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Incubation Time:24 h
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Result:Induced degradation of BRD4 (S), BRD3, and BRD2.
Showed enhanced activity against BRD4 (L) compared to HT29 cells.
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Cell Line:HT29 colorectal cancer cells, PNT2 normal prostatic epithelial cells
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Concentration:0.021-10 μM
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Incubation Time:72 h
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Result:Inhibited HT29 cell proliferation with a GI50 of 4.5 μM.
Did not suppress proliferation of PNT2 cells at any tested concentration.
Chemical Information
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Molecular Weight 1092.87
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Formula C59H82ClN11O5S
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SMILES
CC1=NN=C2[C@@H](N=C(C3=C(N21)SC(C)=C3C)C4=CC=C(C=C4)Cl)CC(NCCCCCCCCCCNC(CCCN5CCC(NC6=C7C=C(OC)C(OCCCN8CCCC8)=CC7=NC(N9CCOCC9)=C6)CC5)=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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS479 Related Classifications
HY-176035 Related Classifications
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