PROTAC SMARCA2/4 degrader-38
Based on 1 Customer Validation
PROTAC SMARCA2/4 degrader-38 is a SMARCA2/4 degrader (SMARCA2: DC50 = 3.0 nM; SMARCA4: 4.0 nM). PROTAC SMARCA2/4 degrader-38 binds to SMARCA2 and SMARCA4 bromodomains to induce degradation via the ubiquitin-proteasome system. PROTAC SMARCA2/4 degrader-38 induces G0/G1 phase cell cycle arrest and cell apoptosis in hematological cancer cells, blocks oncogenic activity of MYC and other disease-related genes in acute myeloid leukemia cells and inhibits proliferation of hematological cancer cell lines. PROTAC SMARCA2/4 degrader-38 can be used for the research of acute myeloid leukemia, diffuse large B-cell lymphoma, breast cancer, ovarian cancer, colorectal cancer, liver cancer, lung cancer.
(Pink: SMARCA2 and SMARCA4 Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker).
For research use only. We do not sell to patients.
- Purity: 99.46%
- CAS No.: 3081688-77-6
- Formula: C43H47N7O5S
- Molecular Weight:773.94
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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SMARCA2 3.0 nM (DC50) |
SMARCA4 4.0 nM (DC50) |
VHL |
PROTAC SMARCA2/4 degrader-38 (compound A11) moderately inhibits SMARCA2 (IC50 = 251 nM) and SMARCA4 (IC50 = 267 nM) bromodomains in a cell-free biochemical assay[1].
PROTAC SMARCA2/4 degrader-38 (≥ 3.7-1000 nM; 0.25-24 h) potently and selectively degrades SMARCA2 and SMARCA4 in a dose- and time-dependent manner, with DC50 values < 10 nM in MV-4-11 and MOLM-13 acute myeloid leukemia cells[1].
PROTAC SMARCA2/4 degrader-38 (100 nM; 6 h) selectively degrades SMARCA2, SMARCA4, and PBRM1 in MV-4-11 acute myeloid leukemia cells with no significant off-target effects across 8569 identified proteins[1].
PROTAC SMARCA2/4 degrader-38 (11.1-1000 nM; 24-72 h) induces SMARCA2/4 degradation in MOLM-13 acute myeloid leukemia cells via binding to SMARCA2/4 bromodomains and the ubiquitin-proteasome pathway, with no effect on SMARCA2/4 mRNA transcription[1].
PROTAC SMARCA2/4 degrader-38 (1-10000 nM) potently inhibits purified SMARCA2/4 bromodomain activity in a concentration-dependent manner in an HTRF assay[1].
PROTAC SMARCA2/4 degrader-38 (72 h) potently inhibits proliferation of acute myeloid leukemia (MV-4-11 IC50 = 0.0049 μM, MOLM-13 IC50 = 0.0233 μM) and diffuse large B-cell lymphoma cell lines, with weaker to no activity against most solid tumor cell lines[1].
PROTAC SMARCA2/4 degrader-38 (100 nM; 3-7 days) inhibits proliferation of MV-4-11 and MOLM-13 acute myeloid leukemia cells in a time-dependent manner, with near-complete inhibition by day 7[1].
PROTAC SMARCA2/4 degrader-38 (11.1-1000 nM; 24 h) downregulates MYC expression and represses transcription of MYC-regulated and AML-related oncogenes in a concentration-dependent manner in MV-4-11 acute myeloid leukemia cells[1].
PROTAC SMARCA2/4 degrader-38 (100-1000 nM; 48 h) induces concentration-dependent G0/G1 phase cell cycle arrest in MV-4-11 and MOLM-13 acute myeloid leukemia cells after 48 h of treatment[1].
PROTAC SMARCA2/4 degrader-38 (100-1000 nM; 72 h) induces apoptosis in MV-4-11 and MOLM-13 acute myeloid leukemia cells in a dose-dependent manner, accompanied by upregulation of cleaved PARP and cleaved caspase-3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:acute myeloid leukemia cell lines MV-4-11, MOLM-13
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Concentration:100 nM
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Incubation Time:3, 5, 7 days
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Result:Significantly reduced viable cell counts in MV-4-11 and MOLM-13 cells by day 3.
Sustained proliferation inhibition through days 5 and 7.
Achieved almost complete proliferation inhibition by day 7.
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Cell Line:acute myeloid leukemia cell lines MV-4-11, MOLM-13
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Concentration:≥ 3.7 nM, 1000 nM (24 h incubation); 100 nM (time-course analysis)
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Incubation Time:24 h (dose-dependent assay); 0.25, 0.5, 1, 2 h (time-course analysis)
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Result:Achieved a DC50 of 3.0 nM (Dmax = 98%) for SMARCA2 in MV-4-11 cells.
Achieved a DC50 of 4.0 nM (Dmax = 98%) for SMARCA4 in MV-4-11 cells.
Achieved a DC50 of 6.0 nM (Dmax = 85%) for SMARCA2 in MOLM-13 cells.
Achieved a DC50 of 8.0 nM (Dmax = 95%) for SMARCA4 in MOLM-13 cells.
Showed no hook effect at 1000 nM.
Induced slight downregulation of SMARCA2/4 at 0.25 and 0.5 h with 100 nM treatment.
Induced significant reduction of SMARCA2/4 by 1 h with 100 nM treatment.
Induced complete abolition of SMARCA2/4 by 2 h with 100 nM treatment.
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Cell Line:acute myeloid leukemia cell lines MV-4-11, MOLM-13
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Concentration:100, 300, 1000 nM
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Incubation Time:48 h
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Result:Induced concentration-dependent G0/G1 phase cell cycle arrest in MV-4-11 cells.
Induced concentration-dependent G0/G1 phase cell cycle arrest in MOLM-13 cells.
Increased accumulation of cells in G0/G1 as concentrations increased from 100 nM to 1000 nM.
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Cell Line:acute myeloid leukemia cell lines MV-4-11, MOLM-13
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Concentration:100, 300, 1000 nM
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Incubation Time:72 h
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Result:Induced significant apoptosis at all tested concentrations, with levels comparable to reference degrader AU-15330.
Upregulated cleaved poly ADP-ribose polymerase (PARP) in a dose-dependent manner.
Upregulated cleaved caspase-3 in a dose-dependent manner.
Chemical Information
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CAS No. 3081688-77-6
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Appearance Solid
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Molecular Weight 773.94
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Formula C43H47N7O5S
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Color Off-white to light yellow
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SMILES
O=C([C@H]1N(C([C@@H](NC(C2(C3=CC=C(C4=CC(C5=CC=CC=C5O)=NN=C4N)C=C3)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)N[C@H](C6=CC=C(C7=C(C)N=CS7)C=C6)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 100 mg/mL (129.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (282 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.2921 mL | 6.4604 mL | 12.9209 mL | 32.3022 mL |
| 5 mM | 0.2584 mL | 1.2921 mL | 2.5842 mL | 6.4604 mL | |
| 10 mM | 0.1292 mL | 0.6460 mL | 1.2921 mL | 3.2302 mL | |
| 15 mM | 0.0861 mL | 0.4307 mL | 0.8614 mL | 2.1535 mL | |
| 20 mM | 0.0646 mL | 0.3230 mL | 0.6460 mL | 1.6151 mL | |
| 25 mM | 0.0517 mL | 0.2584 mL | 0.5168 mL | 1.2921 mL | |
| 30 mM | 0.0431 mL | 0.2153 mL | 0.4307 mL | 1.0767 mL | |
| 40 mM | 0.0323 mL | 0.1615 mL | 0.3230 mL | 0.8076 mL | |
| 50 mM | 0.0258 mL | 0.1292 mL | 0.2584 mL | 0.6460 mL | |
| 60 mM | 0.0215 mL | 0.1077 mL | 0.2153 mL | 0.5384 mL | |
| 80 mM | 0.0162 mL | 0.0808 mL | 0.1615 mL | 0.4038 mL | |
| 100 mM | 0.0129 mL | 0.0646 mL | 0.1292 mL | 0.3230 mL |
PROTAC SMARCA2/4 degrader-38 Related Classifications
HY-173333 Related Classifications
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