PROTAC SMARCA2/4 degrader-26
PROTAC SMARCA2/4 degrader-26 is a SMARCA2/4 PROTAC degrader with selective anti-tumor activity against lung cancer cells. PROTAC SMARCA2/4 degrader-26 degrades SMARCA2 and SMARCA4 via the PROTAC-mediated proteasomal pathway. It induces DNA damage and apoptosis in tumor cells, while inhibiting migration and colony formation of lung cancer cells; in addition, it damages normal vascular endothelial cells and exhibits significant off-target-related cytotoxicity. PROTAC SMARCA2/4 degrader-26 serves as the parent scaffold to construct the GSH-responsive prodrug PROTAC SMARCA2/4 degrader-25 (HY-162813), a derivative that shows drastically reduced cytotoxicity against normal cells. PROTAC SMARCA2/4 degrader-26 can be used in lung cancer-related research.
(Pink: SMARCA2 and SMARCA4 ligand (HY-46618); Blue: Cereblon ligand (HY-W998248); Black: linker (HY-59140)).
For research use only. We do not sell to patients.
- Formula: C38H47N9O5S
- Molecular Weight:741.90
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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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Help & FAQs
Biological Activity
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SMARCA2 |
SMARCA4 |
PROTAC SMARCA2/4 degrader-26 (compound 6) (1 μM; 2-24 h) efficiently degrades SMARCA2 and SMARCA4 in HULEC-5a and HEK 293T cells in a time-dependent manner; it efficiently degrades SMARCA2 in A549 and H1299 lung cancer cells in a time-dependent manner[1].
PROTAC SMARCA2/4 degrader-26 (1 μM; 8 h) mediates the degradation of SMARCA2 in A549 cells in a manner dependent on the 26S proteasome and Cullin-RING E3 ubiquitin ligase pathways[1].
PROTAC SMARCA2/4 degrader-26 (0.1-5 μM; 8 h) does not degrade SMARCA2 or SMARCA4 in 786-O VHL-mutant cells, which confirms its dependence on functional VHL E3 ligase[1].
PROTAC SMARCA2/4 degrader-26 (0.1-2 μM; 8 h) mediates SMARCA2 degradation in H1299 cells, and this degradation activity relies on functional VHL E3 ligase, which disappears completely in VHL-knockdown cells[1].
PROTAC SMARCA2/4 degrader-26 (administered for 5 days) potently inhibits the viability of A549 and H1299 lung cancer cells, with IC50 values of 1.3 μM and 1.4 μM, respectively; after 5 days of incubation, this compound exhibits cytotoxicity against normal HULEC-5a cells, with an IC50 of 24.5 μM[1].
PROTAC SMARCA2/4 degrader-26 (10 μM; 36 h) significantly inhibits the migration ability of A549 lung cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK 293T normal cells
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Concentration:1 μM
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Incubation Time:2 h, 4 h, 8 h, 12 h, 24 h
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Result:Induced time-dependent degradation of SMARCA2 and SMARCA4.
Decreased SMARCA2 levels to 0.04 (normalized to β-Actin) at 24 h.
Decreased SMARCA4 levels to 0.09 (normalized to β-Actin) at 24 h.
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Cell Line:HULEC-5a normal lung microvascular endothelial cells
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Concentration:1 μM
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Incubation Time:2 h, 4 h, 8 h, 12 h, 24 h
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Result:Induced time-dependent degradation of SMARCA2 and SMARCA4.
Decreased SMARCA2 levels to 0.64 (normalized to β-Actin) at 24 h.
Decreased SMARCA4 levels to 0.35 (normalized to β-Actin) at 24 h.
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Cell Line:A549 SMARCA4-deficient lung cancer cells
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Concentration:1 μM
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Incubation Time:2 h, 4 h, 8 h, 12 h, 24 h
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Result:Induced time-dependent degradation of SMARCA2.
Decreased SMARCA2 levels to 0.15 (normalized to β-Actin) at 12 h.
Increased SMARCA2 levels slightly to 0.28 (normalized to β-Actin) at 24 h.
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Cell Line:H1299 SMARCA4-deficient lung cancer cells
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Concentration:1 μM
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Incubation Time:2 h, 4 h, 8 h, 12 h, 24 h
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Result:Induced time-dependent degradation of SMARCA2.
Decreased SMARCA2 levels to 0.02 (normalized to β-Actin) at 24 h.
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Cell Line:A549 SMARCA4-deficient lung cancer cells
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Concentration:1 μM
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Incubation Time:8 h
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Result:Blocked SMARCA2 degradation completely by pretreatment with MG132 (HY-13259) or MLN4924 (HY-70062).
Maintained SMARCA2 levels at 0.88 (normalized to β-Actin) with MG132 pretreatment.
Maintained SMARCA2 levels at 0.88 (normalized to β-Actin) with MLN4924 pretreatment.
Reduced SMARCA2 levels to 0.34 (normalized to β-Actin) without inhibitor pretreatment.
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Cell Line:786-O VHL-mutated renal cell carcinoma cells
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Concentration:0.1, 0.2, 1, 2, 5 μM
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Incubation Time:8 h
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Result:Observed no degradation of SMARCA2 or SMARCA4 at any tested concentration.
Maintained SMARCA2 levels between 0.93 and 1.08 (normalized to β-Actin).
Maintained SMARCA4 levels between 0.72 and 1.07 (normalized to β-Actin).
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Cell Line:H1299 SMARCA4-deficient lung cancer cells (shVHL and shLuc)
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Concentration:0.1, 0.5, 1, 2 μM
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Incubation Time:8 h
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Result:Suppressed SMARCA2 degradation significantly in VHL-knockdown cells compared to control cells.
Decreased SMARCA2 levels to 0.16 in control cells.
Maintained SMARCA2 levels at 0.69 in VHL-knockdown cells.
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Cell Line:A549 SMARCA4-deficient lung cancer cells
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Concentration:10 μM
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Incubation Time:3 days prior to scratching, then 36 h post-scratching
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Result:Markedly inhibited A549 cell migration.
Reduced relative cell migration to approximately 40% of control levels.
Chemical Information
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Molecular Weight 741.90
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Formula C38H47N9O5S
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SMILES
O=C([C@H]1N(C([C@@H](NC(CN2CCN(C3=CC(C4=CC=CC=C4O)=NN=C3N)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC5=CC=C(C6=C(C)N=CS6)C=C5
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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 SMARCA2/4 degrader-26 Related Classifications
HY-162815 Related Classifications
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