PROTAC BET Degrader-15
PROTAC BET Degrader-15 is a BET PROTAC degrader with DC50 values of <0.10 nM, <0.01 nM, and <0.01 nM against BRD2, BRD3, and BRD4, respectively. PROTAC BET Degrader-15 induces significant G2/M phase cell cycle arrest and triggers apoptosis. PROTAC BET Degrader-15 causes marked downregulation of c-Myc, accompanied by upregulation of the cell cycle inhibitory protein p21, downregulation of CDK6, and an increase in the apoptosis marker cleaved PARP. PROTAC BET Degrader-15 is applicable to the research of hematologic malignancies and lung cancer.
(Pink: BRD2 and BRD3 and BRD4 ligand (HY-181735); Blue: Cereblon ligand (HY-41547); Black: linker (HY-33846)).
For research use only. We do not sell to patients.
- Formula: C44H45N9O6
- Molecular Weight:795.88
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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
- Purity & Documentation
- References
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Biological Activity
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BRD2 ＜0.10 nM (DC50) |
BRD3 ＜0.01 nM (DC50) |
BRD4 ＜0.01 nM (DC50) |
CDK6 |
PROTAC BET Degrader-15 (Compound CR10) (72 h) potently inhibits the proliferation of MV4-11, Molm-13, and HL-60 acute myeloid leukemia cells, with IC50 values of 1.21, 2.14, and 0.69 nM respectively[1].
PROTAC BET Degrader-15 (72 h) potently inhibits the proliferation of multiple solid tumor cell lines, with IC50 values ranging from 2.83 nM (MDA-MB-231) to 254.2 nM (A549)[1].
PROTAC BET Degrader-15 (5-20 nM; 2 h) induces degradation of BRD2, BRD3, and BRD4 in MV4-11 and A549 cells via a ubiquitin-proteasome system-dependent mechanism that relies on CRBN and BET protein binding[1].
PROTAC BET Degrader-15 (1 h) binds to BRD2, BRD3, and BRD4 bromodomains with nanomolar affinity, with IC50 values ranging from 22 nM (BRD3(1)) to 61 nM (BRD4(2))[1].
PROTAC BET Degrader-15 (1-50 nM; 24 h) dose-dependently arrests MV4-11 cells at the G2/M phase of the cell cycle after 24 h of treatment[1].
PROTAC BET Degrader-15 (1-20 nM; 24 h) dose-dependently induces apoptosis in MV4-11 cells, with significant apoptosis observed at concentrations as low as 1 nM after 24 h of treatment[1].
PROTAC BET Degrader-15 (3.3-1000 nM; 24 h) modulates key proteins involved in proliferation, cell cycle regulation, and apoptosis in MV4-11, A549, and MDA-MB-231 cells, including downregulating C-Myc and CDK6, upregulating P21, and inducing PARP cleavage[1].
PROTAC BET Degrader-15 (4-50 nM; 8 d) potently inhibits the colony-forming ability of A549 and MDA-MB-231 solid tumor cells, with near-complete inhibition observed at 10 nM[1].
PROTAC BET Degrader-15 (50-100 nM; 0-12 h) potently inhibits the migratory capacity of MDA-MB-231 breast cancer cells at concentrations of 50 and 100 nM[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 and A549 cells
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Concentration:5 nM (MV4-11 cells, 2 h); 20 nM (A549 cells, 2 h); 10 μM MG132, 10 μM Pomalidomide, 10 μM MLN4924, 100 nM compound 10 (2 h pretreatment)
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Incubation Time:2 h (PROTAC BET Degrader-15 treatment); 2 h (pretreatment prior to PROTAC BET Degrader-15 addition)
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Result:Had induced degradation of BRD2, BRD3, and BRD4 completely abolished by pretreatment with MG132, Pomalidomide, MLN4924, or compound 10 in both MV4-11 and A549 cells.
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Cell Line:MV4-11 cells
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Concentration:1, 5, 20 and 50 nM
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Incubation Time:24 h
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Result:Induced a significant, dose-dependent arrest at the G2/M phase of the cell cycle.
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Cell Line:MV4-11 cells
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Concentration:1, 5 and 20 nM
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Incubation Time:24 h
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Result:Elicited pronounced pro-apoptotic effects starting at 1 nM, with apoptosis increasing in a dose-dependent manner.
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Cell Line:MV4-11, A549, and MDA-MB-231 cells
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Concentration:3.3, 10, 100, 200 and 1000 nM
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Incubation Time:24 h
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Result:Caused dose-dependent downregulation of C-Myc and CDK6, upregulation of P21, and an increase in cleaved-PARP levels (with a corresponding decrease in full-length PARP) in all three cell lines.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:50 and 100 nM
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Incubation Time:0, 6, 12 h post-treatment monitoring
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Result:Significantly suppressed cell migration relative to controls, as measured by reduced wound closure over time.
| Species | Dose | Route | T1/2 | Cmax | Vss | MRT0-inf | CL | AUC0-t | AUC0-∞ | Tmax | CL/F | Vz/F | Bioavailability |
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| Mice[1] | 1 mg/kg | i.v. | 1.88 h | 207.14 ng/mL | 0.75 L/kg | 2.62 h | 0.28 L/h/kg | 204.05 ng·h/mL | 215.32 ng·h/mL | / | / | / | / |
| Mice[1] | 20 mg/kg | i.p. | 4.26 h | 778.68 ng/mL | / | 5.10 h | / | 4571.49 ng·h/mL | 4662.67 ng·h/mL | 2.00 h | 3.98 mL/min/kg | 1.45 L/kg | 108.27 % |
| Mice[1] | 20 mg/kg | p.o. | 0.92 h | 350.49 ng/mL | / | 1.38 h | / | 496.20 ng·h/mL | 529.67 ng·h/mL | 0.33 h | 40.02 mL/min/kg | 3.13 L/kg | 12.30 % |
PROTAC BET Degrader-15 (1-2 mg/kg; i.p.; once every 4 days for 17 days total) induces dose-dependent tumor growth inhibition in MV4-11 xenograft mice[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 (female, 6-8 weeks old)[1]
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Dosage:1 mg/kg; 2 mg/kg
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Administration:i.p.; every 4 days; 21 days
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Result:Induced tumor growth inhibition rate of 54.74% at 1 mg/kg and 72.97% at 2 mg/kg, which were notably higher than the positive control dBet1.
Maintained largely unchanged body weights throughout the study.
Showed no obvious lesions in major organs (heart, liver, spleen, lung, kidney) via histopathological examination.
Showed no significant abnormalities in hematological and biochemical analyses.
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Animal Model:BALB/c nude (female, 6-8 weeks old)[1]
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Dosage:1 mg/kg; 2 mg/kg
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Administration:i.p.; every 4 days; 17 days
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Result:Induced tumor growth inhibition rates of 44.26% at 1 mg/kg and 63.19% at 2 mg/kg, which were higher than the positive control dBet1.
Maintained largely unchanged body weights throughout the study.
Showed no obvious lesions in major organs (heart, liver, spleen, lung, kidney) via histopathological examination.
Showed no significant abnormalities in hematological and biochemical analyses.
Chemical Information
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Molecular Weight 795.88
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Formula C44H45N9O6
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SMILES
COC1=C(C2=C(C)ON=C2C)C=C3C(C(N([C@@H](C4=CC=CC=C4)C)C(CN5CCN(CCNC6=C7C(C(N(C8CCC(NC8=O)=O)C7=O)=O)=CC=C6)CC5)=N9)=C9C=N3)=C1
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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-15 Related Classifications
HY-181729 Related Classifications
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