PROTAC SMARCA2/4 degrader-25
PROTAC SMARCA2/4 degrader-25 is a selective SMARCA2/SMARCA4 PROTAC degrader with selective anti-tumor activity. PROTAC SMARCA2/4 degrader-25 is activated by endogenous GSH, forms a ternary complex with SMARCA2 or SMARCA4 and VHL E3 ubiquitin ligase, and mediates degradation via the proteasome pathway. PROTAC SMARCA2/4 degrader-25 induces DNA damage and apoptosis, and inhibits cancer cell proliferation. PROTAC SMARCA2/4 degrader-25 is applicable to lung cancer-related research.
(Pink: SMARCA2 and SMARCA4 ligand (HY-162814); Blue: Cereblon ligand (HY-W998248); Black: linker (HY-59140)).
For research use only. We do not sell to patients.
- Formula: C44H50N10O9S2
- Molecular Weight:927.06
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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-25 (compound 7d) (50 μM; up to 50 h) is stable in PBS buffer, and reacts rapidly with glutathione (GSH) in a cell-free system to release the active PROTAC 6[1].
PROTAC SMARCA2/4 degrader-25 (1 μM; 0-24 h) selectively degrades SMARCA2 in a GSH-dependent manner in SMARCA4-deficient A549 and H1299 lung cancer cells, but exerts no such effect in normal HEK 293T or HULEC-5a cells[1].
PROTAC SMARCA2/4 degrader-25 (0-1000 μM; 3-8 h) mediates the degradation of SMARCA2 in A549 and H1299 cells via the canonical PROTAC mechanism dependent on the VHL E3 ligase and the ubiquitin-proteasome system[1].
PROTAC SMARCA2/4 degrader-25 (5 days) selectively inhibits the viability of SMARCA4-deficient A549 and H1299 lung cancer cells with IC50 values of 9.1 μM and 21.8 μM, respectively, while exerting no significant cytotoxicity against normal HULEC-5a lung cells[1].
PROTAC SMARCA2/4 degrader-25 (10 μM; 3 days + 36 h) potently inhibits migration of SMARCA4-deficient A549 lung cancer cells[1].
PROTAC SMARCA2/4 degrader-25 (0-20 μM; 13 days) selectively inhibits the proliferation of SMARCA4-deficient 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, HULEC-5a, A549, H1299
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Concentration:1 μM;
100 μM NEM (HY-D0843) (pre-treatment) -
Incubation Time:0 h, 2 h, 4 h, 8 h, 12 h, 24 h
4 h (NEM pre-incubation) -
Result:Caused negligible degradation of SMARCA2/4 over 24 h in HEK 293T and HULEC-5a cells.
Induced time-dependent SMARCA2 degradation in A549 cells, reducing levels to 19% of baseline by 8 h and 42% by 24 h.
Induced time-dependent SMARCA2 degradation in H1299 cells, reducing levels to 54% of baseline by 24 h.
Pretreatment with NEM completely abolished 7d-induced SMARCA2 degradation in A549 cells.
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Cell Line:A549, 786-O, H1299
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Concentration:1 μM (7d, A549); 10 μM MG132 (HY-13259); 3 μM MLN4924 (HY-70062)
0.1, 0.5, 1, 2, 5 μM (7d, 786-O)
0.1, 0.5, 1, 2 μM (7d, H1299) -
Incubation Time:8 h (7d, A549)
3 h (MG132/MLN4924 pre-incubation)
8 h (7d, 786-O/H1299) -
Result:Pretreatment with MG132 or MLN4924 completely blocked PROTAC SMARCA2/4 degrader-25-induced SMARCA2 degradation in A549 cells.
Caused no SMARCA2/4 degradation in VHL-mutated 786-O cells.
VHL knockdown in H1299 cells significantly suppressed PROTAC SMARCA2/4 degrader-25-induced SMARCA2 degradation compared to control shLuc cells.
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Cell Line:A549
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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:Significantly inhibited the migration of A549 cells compared to untreated control cells.
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Cell Line:A549, HULEC-5a
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Concentration:0, 0.8, 4, 20 μM
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Incubation Time:13 days
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Result:Caused a dramatic dose-dependent reduction in colony number and size in A549 cells, with nearly complete inhibition at 20 μM.
Had no effect on colony formation in HULEC-5a cells even at 20 μM.
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, subcutaneous xenograft model via injection of 5×106 A549 cells)[1]
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Dosage:80 mg/kg
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Administration:intratumoral injection; every 4 days
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Result:Significantly reduced tumor burden and size, with antitumor efficacy becoming more pronounced after the fourth treatment.
Decreased tumor weight significantly compared to vehicle controls at study end.
Suppressed SMARCA2 protein levels to 0.39 relative to vehicle controls.
Increased cleaved-Caspase-3 levels to 2.33 relative to vehicle controls.
Reduced SMARCA2 H-scores, increased cleaved-Caspase-3 H-scores, reduced Ki67 H-scores, and increased γ-H2AX H-scores (all p < 0.001).
Showed no signs of toxicity to heart, liver, spleen, lung, and kidney via H&E staining.
Left mouse body weight unchanged.
Chemical Information
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Molecular Weight 927.06
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Formula C44H50N10O9S2
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SMILES
O=S(C1=CC=C([N+]([O-])=O)C=C1)(OC2=CC=CC=C2C3=NN=C(N)C(N4CCN(CC(N[C@@H](C(C)(C)C)C(N5[C@H](C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@@H](O)C5)=O)=O)CC4)=C3)=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 SMARCA2/4 degrader-25 Related Classifications
HY-162813 Related Classifications
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