PROTAC SMARCA2/4 degrader-36
PROTAC SMARCA2/4 degrader-36 is a bifunctional PROTAC degrader that degrades SMARCA2 and SMARCA4. PROTAC SMARCA2/4 degrader-36 hijacks the ubiquitin-proteasome system to mediate the degradation of SMARCA2/4 by binding to the VHL E3 ubiquitin ligase. PROTAC SMARCA2/4 degrader-36 downregulates SMARCA2/4 in tumor tissues in mouse xenograft models. PROTAC SMARCA2/4 degrader-36 can be used in studies related to non-small cell lung cancer.
(Pink: SMARCA2 and SMARCA4 ligand (HY-170354); Blue: VHL ligand (HY-170353); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3033588-00-7
- Formula: C53H62ClN9O4S
- Molecular Weight:956.64
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
SMARCA2 0.22 nM (DC50) |
SMARCA4 0.85 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HT-1080 | DC50 |
0.22 nM
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Degradation of SMARCA2 protein in HT1080 cells genetically modified to express SMARCA2-HiBiT, assessed using Nano-Glo HiBiT Lytic Detection Assay after 6 h incubation.
Degradation of SMARCA2 protein in HT1080 cells genetically modified to express SMARCA2-HiBiT, assessed using Nano-Glo HiBiT Lytic Detection Assay after 6 h incubation.
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39570797 |
| HT-1080 | DC50 |
0.85 nM
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Degradation of SMARCA4 protein in HT1080 cells genetically modified to express SMARCA4-HiBiT, assessed using Nano-Glo HiBiT Lytic Detection Assay after 6 h incubation.
Degradation of SMARCA4 protein in HT1080 cells genetically modified to express SMARCA4-HiBiT, assessed using Nano-Glo HiBiT Lytic Detection Assay after 6 h incubation.
|
39570797 |
In Vitro
PROTAC SMARCA2/4 degrader-36 (compound 29) binds to VHL E3 ubiquitin ligase with an IC50 of 2.1 nM[1].
PROTAC SMARCA2/4 degrader-36 potently degrades SMARCA2 (DC50 = 0.22 nM, Dmax = 98%) and SMARCA4 (DC50 = 0.85 nM, Dmax = 97%) in HT1080 cells[1].
PROTAC SMARCA2/4 degrader-36 potently inhibits the proliferation of SMARCA4-deficient NCIH838 cells (gIC50 = 3.0 nM) and SMARCA4 wild-type Calu-6 cells (gIC50 = 280 nM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c Nude mice were subcutaneously inoculated with HT‑1080 tumor cells (2 × 106 cells per mouse in 0.1 mL PBS)[1]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:i.v.; single dose
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Result:Reduced SMARCA2 protein levels in tumor tissue by 94% and SMARCA4 protein levels by 54% relative to vehicle control.
Reduced SMARCA2 protein levels by >95% and SMARCA4 protein levels by 93% relative to vehicle control.
Chemical Information
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CAS No. 3033588-00-7
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Molecular Weight 956.64
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Formula C53H62ClN9O4S
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SMILES
ClC1=CC=CC(N(C(C=CC(C2CCN(C[C@H]3CC[C@H](C4=CN([C@H](C(N5C[C@H](O)C[C@H]5C(N[C@@H](C)C6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)C(C)C)N=N4)CC3)CC2)=C8)=C8C9(C)C)C9=N%10)=C1C%10=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.
Protocols
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)