PROTAC BRD4 Degrader-27
PROTAC BRD4 Degrader-27 is a selective cereblon-mediated BRD4 PROTAC degrader. PROTAC BRD4 Degrader-27 exhibits anticancer activity, induces G1 phase arrest, and inhibits DNA synthesis and colony formation. PROTAC BRD4 Degrader-27 suppresses HCC1806 tumor growth in xenograft mouse models. PROTAC BRD4 Degrader-27 can be used in breast cancer-related research.
(Pink: BRD4 ligand (HY-162876); Blue: Cereblon ligand (HY-103596); Black: linker (HY-N0067)).
For research use only. We do not sell to patients.
- CAS No.: 2407163-44-2
- Formula: C37H30F2N6O7
- Molecular Weight:708.67
-
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]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
|
BRD4 |
Cdk4/cyclin D1 |
PROTAC BRD4 Degrader-27 (compound 6b) (0.001-1 μM; 0-48 h) efficiently and selectively degrades BRD4 (but not BRD2 or BRD3) in a dose- and time-dependent manner in HCC1806 and HCC1937 basal-like breast cancer (BLBC) cells, thereby shortening the half-life of BRD4 and altering the expression of BRD4 downstream target proteins[1].
PROTAC BRD4 Degrader-27 (0.2-3.2 μM; 4 days) inhibits the growth of HCC1806, HCC1937, Hs578T, MDA-MB-231 and SUM149PT BLBC cells in a dose-dependent manner, with an IC50 value of 1.3 μM against HCC1806 and 1.7 μM against HCC1937[1].
PROTAC BRD4 Degrader-27 (0.05-0.2 μM; 9 days) potently inhibits colony formation of HCC1806 and HCC1937 basal-like breast cancer (BLBC) cells[1].
PROTAC BRD4 Degrader-27 (0.5-1 μM; 8 h, 48 h) promotes proteasome-dependent ubiquitination and degradation of BRD4 in HCC1806, HCC1937 and HEK293T cells[1].
PROTAC BRD4 Degrader-27 (0.05-1.6 μM; 48 h)-mediated BRD4 degradation and growth inhibition in HCC1806 and HCC1937 basal-like breast cancer (BLBC) cells are dependent on CRBN; CRBN knockdown blocks BRD4 degradation and significantly reduces cytotoxicity[1].
PROTAC BRD4 Degrader-27 (0.05-0.2 μM; 48 h) induces dose-dependent G1-phase cell cycle arrest in HCC1806 and HCC1937 basal-like breast cancer (BLBC) cells by downregulating cyclinD1 expression and upregulating p21 and p27 expression; it also inhibits DNA synthesis and reduces the proportion of proliferating cells in a dose-dependent manner[1].
PROTAC BRD4 Degrader-27 (0.01-1.6 μM; 48 h) induces cell cycle arrest and growth inhibition in HCC1806 and HCC1937 basal-like breast cancer (BLBC) cells primarily dependent on BRD4 degradation, as overexpression of BRD4 reverses these effects; it partially inhibits cell proliferation by downregulating KLF5; overexpression of KLF5 reverses this proliferation inhibition, while knockdown of KLF5 enhances cellular sensitivity to this compound[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HCC1806, HCC1937 basal-like breast cancer (BLBC) cell lines
-
Concentration:0.001, 0.01, 0.1, 1 μM (48 h incubation)
0.1 μM (0-48 h incubation)
0.1 μM (12 h pre-incubation for cycloheximide chase)
0.5, 1 μM (48 h incubation) -
Incubation Time:48 h (0.001-1 μM, 0.5-1 μM)
0, 3, 12, 24, 36, 48 h (0.1 μM)
12 h (0.1 μM pre-incubation) followed by 0, 1, 2, 4 h cycloheximide treatment -
Result:Potently and selectively degraded BRD4 protein, with no effect on BRD2 or BRD3.
Achieved near-complete depletion of BRD4 at 0.01 μM in HCC1806 cells and 0.1 μM in HCC1937 cells after 48 h.
Degraded most BRD4 within 12 h in both cell lines at 0.1 μM.
Accelerated BRD4 degradation, markedly reducing the protein's half-life in cycloheximide chase experiments.
Caused a marked decline in BRD4 downstream targets KLF5, c-Myc, SKP2, Bcl-2, and Bcl-XL after 48 h treatment.
Increased levels of Bim, p21, and p27 after 48 h treatment.
-
Cell Line:HCC1806, HCC1937, Hs578T, MDA-MB-231, SUM149PT BLBC cell lines
-
Concentration:0.2, 0.4, 0.8, 1.6, 3.2 μM
-
Incubation Time:4 days
-
Result:Exhibited a half-maximal inhibitory concentration (IC50) of 1.3 μM in HCC1806 cells.
Exhibited a half-maximal inhibitory concentration (IC50) of 1.7 μM in HCC1937 cells.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.05, 0.2 μM
-
Incubation Time:48 h
-
Result:Increased the proportion of cells in the G1 phase in a dose-dependent manner, inducing G1 phase cell cycle arrest.
Decreased cyclinD1 expression via Western blot analysis.
Increased p21 and p27 levels via Western blot analysis.
Caused no change in CDK4/6 expression via Western blot analysis.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.05, .2 μM
-
Incubation Time:48 h
-
Result:Gradually inhibited DNA synthesis in both cell lines in a dose-dependent manner.
Reduced the percentage of EdU-positive proliferating cells.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.05, 0.2 μM
-
Incubation Time:9 days
-
Result:Strongly reduced colony formation in both cell lines.
Almost eliminated colony formation at 0.05 μM.
-
Cell Line:HEK293T, HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.5, 1 μM
3 μM MG-132 (HY-13259) -
Incubation Time:48 h
8 h MG-132 -
Result:Promoted proteasome-dependent ubiquitination and degradation of BRD4 in HCC1806, HCC1937, and HEK293T cells.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0, 0.01, 0.1 μM
20 μM MG-132 -
Incubation Time:48 h
8 h MG-132 -
Result:Increased the ubiquitination of exogenous and
endogenous BRD4.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.01, 0.1 μM
-
Incubation Time:48 h
-
Result:Reduced the protein abundance of KLF5, C-MYC, FGF-BP1 and Cyclin D1 in a concentration-dependent manner in both pCDH normal cells and BRD4 overexpressing cells.
-
Cell Line:HCC1806, HCC1937 BLBC cell lines
-
Concentration:0.05, 0.1, 0.2 μM
-
Incubation Time:48 h
-
Result:Reversed the elevation of p21 protein expression in a concentration-dependent manner in both pCDH normal cells and BRD4 overexpressing cells.
PROTAC BRD4 Degrader-27 (5-10 mg/kg; i.p.; once every 2 days; for 15 consecutive days) potently inhibits the growth of UM1 basal-like breast cancer PDX tumors in nude mice and reduces the levels of BRD4, KLF5 and Ki-67 in tumor tissues[1].
PROTAC BRD4 Degrader-27 (5 mg/kg; i.p.; once daily for 22 consecutive days) combined with 50 mg/kg FZU-00,004 slightly suppressed the proliferation of HCC1806 basal-like breast cancer xenografts in nude mice, lowered the expression levels of BRD4, KLF5 and Ki-67 within tumour tissues, and did not induce observable body weight fluctuations in experimental nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c nude (female, 4-6 weeks old)[1]
-
Dosage:5 mg/kg; 10 mg/kg
-
Administration:i.p.; once every 2 days; 25 days
-
Result:Significantly reduced tumor volume and weight compared to control.
Resulted in lower final tumor volume and weight at 10 mg/kg than at 5 mg/kg.
Showed no significant changes in mouse body weight at either dose.
-
Animal Model:BALB/c nude (female, 4-6 weeks old)[1]
-
Dosage:5 mg/kg; 10 mg/kg
-
Administration:i.p.; once every 2 days; 15 days
-
Result:Significantly reduced UM1 PDX tumor volume and weight compared to control.
Significantly decreased BRD4, KLF5, and Ki-67 protein levels in tumor tissues at both doses.
Showed no significant changes in mouse body weight at either dose.
Chemical Information
-
CAS No. 2407163-44-2
-
Molecular Weight 708.67
-
Formula C37H30F2N6O7
-
SMILES
CN1C=C(C2=C(C1=O)NC=C2)C3=CC(NC(CCCNC4=CC=CC5=C4C(N(C5=O)C6CCC(NC6=O)=O)=O)=O)=CC=C3OC7=CC=C(C=C7F)F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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 BRD4 Degrader-27 Related Classifications
HY-162875 Related Classifications
Powered by Bioz