PROTAC BRM/BRG1 degrader-3
PROTAC BRM/BRG1 degrader-3 is a BRM/BRG1 PROTAC degrader, exhibiting a DC50 of less than 1 nM for BRM degradation and a DC50 of greater than 1 nM for BRG1 degradation in SW1573 cells. PROTAC BRM/BRG1 degrader-3 shows moderate inhibitory activity against CYP2D6 and hERG. PROTAC BRM/BRG1 degrader-3 inhibits cancer cell proliferation and tumor tissue growth, and exhibits favorable metabolic stability in liver microsomes. PROTAC BRM/BRG1 degrader-3 can be used in non-small cell lung cancer-related research.
(Pink: BRM and BRG1 ligand (HY-168252); Blue: VHL ligand (HY-168253); Black: linker (HY-69260)).
For research use only. We do not sell to patients.
- CAS No.: 2933125-05-2
- Formula: C50H63N11O5S
- Molecular Weight:930.17
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
PROTAC BRM/BRG1 degrader-3 (compound 304) shows BRM degradation activity in A549 cells (BRG1-mutant) and SW1573 cells (DC50 = 0.4 nM and 0.19 nM, Dmax = 67% and 94%, respectively), and BRG1 degradation activity in SW1573 cells (DC50 = 2.3 nM, Dmax = 74%) (specific concentration and time not specified in the original text)[1].
PROTAC BRM/BRG1 degrader-3 shows antiproliferative activity in A549 cells (BRG1-mutant), with an IC50 of 0.6 nM (specific concentration and time not specified in the original text)[1].
PROTAC BRM/BRG1 degrader-3 was not tested for antiproliferative activity in MIA PaCa-2 cells (BRM-mutant)[1].
PROTAC BRM/BRG1 degrader-3 (1 μM; 0.5-60 min) shows metabolic stability in human, Beagle dog, SD rat, and CD-1 mouse liver microsomes, with in vitro half-lives of 89.4, 50.3, 650.0, and 169.2 minutes, and in vitro intrinsic clearances of 15.5, 27.6, 2.1, and 8.2 μL/min/mg protein, respectively[1].
PROTAC BRM/BRG1 degrader-3 (0.02-50 μM) shows inhibitory activity against cytochrome P450 enzymes CYP2C9, CYP2D6, and CYP3A4, with IC50 values of >50 μM, 9 μM, and >50 μM, respectively[1].
PROTAC BRM/BRG1 degrader-3 (0.37-30 μM) shows inhibitory activity against the hERG potassium channel, with an IC50 of 5.7 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | C0 | Vdss | CL | AUC |
|---|---|---|---|---|---|---|---|
| Dog[1] | 1 mg/kg | i.v. | 3.62 h | 722 ng/mL | 5.71 L/kg | 33.9 mL/min/kg | 464 ng·h/mL |
| Mice[1] | 10 mg/kg | i.v. | 5.18 h | 60250 ng/mL | 0.61 L/kg | 5.40 mL/min/kg | 30760 ng·h/mL |
| Monkey[1] | 1 mg/kg | i.v. | 9.4 h | 10455 ng/mL | 3.15 L/kg | 9.75 mL/min/kg | 1606 ng·h/mL |
| Rat[1] | 1 mg/kg | i.v. | 6.69 h | 9402 ng/mL | 0.81 L/kg | 3.93 mL/min/kg | 4560 ng·h/mL |
| Rat[1] | 5 mg/kg | i.v. | 5.53 h | 39936 ng/mL | 0.46 L/kg | 3.5 mL/min/kg | 24232 ng·h/mL |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice (female Balb/c nude mice, 7-9 weeks old, weighing approximately 18-22 g) were subcutaneously inoculated in the right flank with 0.1 mL of a cell suspension containing 5×106 A549 cells (mixed with Matrigel in DPBS at a 1:1 ratio)[1].
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Dosage:40 mg/kg
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Administration:intravenous injection (i.v.); on Day 0 and Day 3
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Result:At Day 0, the mean tumor volume in this compound-treated group was 114.27 mm3, while that in the vehicle control group was 115.25 mm3, indicating that the baseline tumor volumes were comparable between the two groups. At Day 14, the mean tumor volume in this compound-treated group was 116.70 mm3, whereas that in the vehicle control group was 438.47 mm3. This compound-treated group exhibited a tumor growth inhibition (TGI) rate of 99.2%, and showed significantly inhibited tumor growth compared with the vehicle control group. During the dosing period, body weight fluctuations were observed in this compound-treated group, but the body weights recovered after the cessation of dosing, indicating that this dosing regimen was tolerable in mice.
Chemical Information
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CAS No. 2933125-05-2
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Molecular Weight 930.17
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Formula C50H63N11O5S
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SMILES
OC(C=CC=C1)=C1C2=CC3=C(N=N2)C(NC(C)C)=NN3C4CCN(CC5CCN(C6=NOC(C(C(N7C[C@H](O)C[C@H]7C(N[C@@H](C)C8=CC=C(C9=C(C)N=CS9)C=C8)=O)=O)C(C)C)=C6)CC5)CC4
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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 BRM/BRG1 degrader-3 Related Classifications
HY-168251 Related Classifications
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