PROTAC BET Degrader-18
PROTAC BET Degrader-18 is a PROTAC targeting BET, with a DC50 of 0.676 nM in HEK293-BRD4-HiBiT-KI cells. PROTAC BET Degrader-18 mainly targets and degrades BRD4 (EC50 = 59.91 nM), and exhibits weak degradation activity against BRD2. PROTAC BET Degrader-18 inhibits the expression of downstream oncoprotein c-Myc, thereby inducing cell cycle arrest and apoptosis, while suppressing oncoprotein expression. PROTAC BET Degrader-18 shows antiproliferative activity against acute myeloid leukemia cells and triple-negative breast cancer cells. PROTAC BET Degrader-18 demonstrates antitumor efficacy in xenograft mouse models. PROTAC BET Degrader-18 can be used for the research of acute myeloid leukemia and triple-negative breast cancer.
(Pink: BRD4 ligand (HY-184339); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3097564-20-7
- Formula: C51H58N8O11S
- Molecular Weight:991.12
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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
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Biological Activity
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BRD4 59.91 nM (EC50) |
BRD2 |
PROTAC BET Degrader-18 (compound 36) (F364) (50 nM; 48.8 pM-12.8 μM) efficiently promotes the formation of the CRBN::BRD4 BD1 ternary complex, with an EC50 of 59.91 nM[1].
PROTAC BET Degrader-18 (10 μM; 24 h) potently degrades BRD4 in HEK293-BRD4-HiBiT-KI cells, with a Dmax of 93.96% and a DC50 of 0.676 nM[1].
PROTAC BET Degrader-18 (10 μM) potently inhibits the proliferation of MV4-11 wild-type acute myeloid leukemia cells and SHP099-resistant MV4-11 acute myeloid leukemia cells, with IC50 values of 4.99 nM and 1.62 nM, respectively[1].
PROTAC BET Degrader-18 (10 μM; 200 nM) inhibits the proliferation of MDA-MB-231 triple-negative breast cancer cells, with an IC50 of 127.87 nM and an inhibition rate of 54.50% at a concentration of 200 nM[1].
PROTAC BET Degrader-18 (10 nM-5 μM; 48 h) induces CRBN-mediated proteasomal degradation of BRD4 (maximum degradation rate of 88.52%) and downregulates c-Myc (maximum downregulation rate of 83.21%) in MV4-11 acute myeloid leukemia cells following 48 h of treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:10 nM, 50 nM, 200 nM, 1 μM, 5 μM
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Incubation Time:48 h
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Result:Induced CRBN-mediated proteasomal degradation of BRD4 (maximum degradation rate of 88.52%) and downregulates c-Myc (maximum downregulation rate of 83.21%).
PROTAC BET Degrader-18 (5-20 mg/kg; intravenous injection; once every two days; 3 weeks) achieves a tumor growth inhibition rate of 66.83% in the MDA-MB-231 triple-negative breast cancer xenograft model, with no toxicity observed[1].
PROTAC BET Degrader-18 (20 mg/kg; intravenous injection; administered every other day for 2 consecutive weeks) is well tolerated in normal BALB/c mice, with no toxicity observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice were subcutaneously inoculated with MV4-11 cells (1×108 cells/mL, 0.1 mL per mouse) suspended in serum-free medium and Matrigel
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Dosage:5 mg/kg; 20 mg/kg
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Administration:i.v.; every other day; 3 weeks
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Result:Achieved a tumor growth inhibition (TGI) rate of 88.90%.
Reduced BRD4 protein levels in tumor tissues by 84.61%.
Reduced c-Myc expression to 91.40%.
Caused no notable body weight loss or overt clinical abnormalities.
Showed no treatment-related hematotoxicity via routine hematology.
Revealed no significant abnormalities in histopathological examination of major organs (heart, liver, spleen, lung, kidney).
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Animal Model:BALB/c nude mice were subcutaneously inoculated with MDA-MB-231 cells (1×108 cells/mL, 0.1 mL per mouse) suspended in serum-free medium and Matrigel
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Dosage:5 mg/kg; 20 mg/kg
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Administration:i.v.; every other day; 3 weeks
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Result:Achieved a tumor growth inhibition (TGI) rate of 66.83%.
Caused no notable body weight loss or overt clinical abnormalities.
Showed no treatment-related hematotoxicity via routine hematology.
Revealed no significant abnormalities in histopathological examination of major organs (heart, liver, spleen, lung, kidney).
Chemical Information
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CAS No. 3097564-20-7
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Molecular Weight 991.12
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Formula C51H58N8O11S
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SMILES
CC(C1=C(NC(C(NC2=C(C=CC(S(=O)(N3CCOCC3)=O)=C2)OCCCC(N4CCN(CC4)CC5CCN(CC5)C6=CC=C7C(N(C(C7=C6)=O)C8CCC(NC8=O)=O)=O)=O)=O)=C1C9=CC=CC=C9)C)=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)
PROTAC BET Degrader-18 Related Classifications
HY-184335 Related Classifications
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- PROTAC BET Degrader-18
- 3097564-20-7
- PROTAC BET Degrader18
- PROTAC BET Degrader 18
- PROTACs
- Epigenetic Reader Domain
- c-Myc
- Apoptosis
- BRD4
- acute myeloid leukemia cells
- triple-negative breast cancer cells
- ubiquitin-proteasomal pathway
- xenograft mouse models
- cereblon
- CRBN
- HEK293-BRD4-HiBiT-KI cells
- MV4-11 cells
- Inhibitor
- inhibitor
- inhibit