SMD-1087
SMD-1087 is a VHL-recruiting SMARCA2 PROTAC degrader with a DC50 of 8 nM. SMD-1087 induces ubiquitination and degradation of SMARCA2 via the proteasome pathway. SMD-1087 reduces PBRM1 protein levels, inhibits the growth of SMARCA4-deficient cancer cells, and suppresses tumor growth in mouse xenograft models. SMD-1087 can be used for research on SMARCA4-deficient human cancers, including lung cancer and melanoma.
(Pink: SMARCA2 ligand (HY-170817); Blue: VHL ligand (HY-112078); Black: linker (HY-W890392)).
For research use only. We do not sell to patients.
- CAS No.: 3033586-04-5
- Formula: C56H68ClN7O5S
- Molecular Weight:986.70
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[2]|
SMARCA2 8 nM (DC50) |
PBRM1 |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| HeLa | DC50 |
8 nM
|
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
|
39745064 |
| HeLa | DC50 |
> 10000 nM
|
Degradation of SMARCA4 protein in HeLa cells genetically modified to express SMARCA4-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
Degradation of SMARCA4 protein in HeLa cells genetically modified to express SMARCA4-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
|
39745064 |
| HeLa | DC50 |
142 nM
|
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 4 h incubation.
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 4 h incubation.
|
39745064 |
| HeLa | DC50 |
89 nM
|
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 8 h incubation.
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 8 h incubation.
|
39745064 |
| HeLa | DC50 |
49 nM
|
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 24 h incubation.
|
39745064 |
| HeLa | DC50 |
44 nM
|
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 48 h incubation.
Degradation of SMARCA2 protein in HeLa cells genetically modified to express SMARCA2-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 48 h incubation.
|
39745064 |
| HeLa | DC50 |
> 1000 nM
|
Degradation of SMARCA4 protein in HeLa cells genetically modified to express SMARCA4-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 4 to 48 h incubation.
Degradation of SMARCA4 protein in HeLa cells genetically modified to express SMARCA4-HiBiT assessed via Nano-Glo HiBiT Lytic Detection Assay after 4 to 48 h incubation.
|
39745064 |
| SK-MEL-5 | DC50 |
81.1 nM
|
Degradation of SMARCA2 protein in SK-Mel-5 SMARCA4 mutant melanoma cells assessed via Western blot after 24 h incubation.
Degradation of SMARCA2 protein in SK-Mel-5 SMARCA4 mutant melanoma cells assessed via Western blot after 24 h incubation.
|
39745064 |
| NCI-H838 | DC50 |
76.2 nM
|
Degradation of SMARCA2 protein in H838 SMARCA4 mutant lung cancer cells assessed via Western blot after 24 h incubation.
Degradation of SMARCA2 protein in H838 SMARCA4 mutant lung cancer cells assessed via Western blot after 24 h incubation.
|
39745064 |
| NCI-H1792 | DC50 |
100 nM
|
Degradation of PBRM1 protein in H1792 SMARCA4 wild-type cells assessed via Western blot after 24 h incubation.
Degradation of PBRM1 protein in H1792 SMARCA4 wild-type cells assessed via Western blot after 24 h incubation.
|
39745064 |
| NCI-H1792 | GI50 |
> 1000 nM
|
Cell growth inhibition in H1792 SMARCA2/4 wild-type cancer cells assessed via cell viability measurement after 7-day incubation.
Cell growth inhibition in H1792 SMARCA2/4 wild-type cancer cells assessed via cell viability measurement after 7-day incubation.
|
39745064 |
| SK-MEL-28 | GI50 |
> 1000 nM
|
Cell growth inhibition in SK-Mel-28 SMARCA2/4 wild-type cancer cells assessed via cell viability measurement after 7-day incubation.
Cell growth inhibition in SK-Mel-28 SMARCA2/4 wild-type cancer cells assessed via cell viability measurement after 7-day incubation.
|
39745064 |
| NCI-H838 | GI50 |
142 nM
|
Cell growth inhibition in H838 SMARCA4 deficient cancer cells assessed via cell viability measurement after 7-day incubation.
Cell growth inhibition in H838 SMARCA4 deficient cancer cells assessed via cell viability measurement after 7-day incubation.
|
39745064 |
| SK-MEL-5 | GI50 |
22.3 nM
|
Cell growth inhibition in SK-Mel-5 SMARCA4 deficient cancer cells assessed via cell viability measurement after 7-day incubation.
Cell growth inhibition in SK-Mel-5 SMARCA4 deficient cancer cells assessed via cell viability measurement after 7-day incubation.
|
39745064 |
In Vitro
SMD-1087 potently degrades SMARCA2 with a DC50 of 6-13 nM and 88-92% maximum degradation, while being > 1000-fold selective over SMARCA4[1].
SMD-1087 (24 h) potently and selectively degrades SMARCA2 (DC50 = 8 nM, Dmax = 89%) over SMARCA4 (DC50 > 10,000 nM, Dmax = 20%) in modified HeLa cells after 24 h treatment, with > 1,250-fold selectivity[2].
SMD-1087 (4-48 h) induces time-dependent degradation of SMARCA2 in modified HeLa cells, with increasing potency and efficiency over 4 to 24 h, while showing minimal activity against SMARCA4 across all tested treatment durations[2].
SMD-1087 (0.01-1000 nM; 24 h) dose-dependently degrades SMARCA2 but not SMARCA4 in H1792 SMARCA4 wild-type cells after 24 h treatment[2].
SMD-1087 (0.01-1000 nM; 24 h) potently degrades SMARCA2 (DC50 = 81.1 nM, Dmax = 87%) in SK-Mel-5 SMARCA4G12C mutant cells after 24 h treatment[2].
SMD-1087 (0.01-1000 nM; 24 h) potently degrades SMARCA2 (DC50 = 76.2 nM, Dmax = 89%) in H838 SMARCA4 mutant cells after 24 h treatment[2].
SMD-1087 (up to 1 μM; 24 h) degrades PBRM1 (DC50 ~100 nM, Dmax = 62% at 1 μM) in H1792 SMARCA4 wild-type cells after 24 h treatment[2].
SMD-1087 (0.1-1000 nM; 24 h) induces partial PBRM1 protein degradation in H1792 cells at concentrations of 10 nM and above after 24-hour incubation, with maximum degradation observed at 1000 nM.
SMD-1087 (up to 1 μM; 7 days) does not inhibit cell growth in H1792 and SK-Mel-28 SMARCA2/4 wild-type cell lines after 7-day treatment at concentrations up to 1 μM[2].
SMD-1087 (up to 1 μM; 7 days) potently inhibits cell growth in SMARCA4 deficient H838 (GI50 = 142 nM, Imax = 79%) and SK-Mel-5 (GI50 = 22.3 nM, Imax = 93%) cell lines after 7-day treatment[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:H1792 SMARCA4 wild-type cells
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM
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Incubation Time:24 h
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Result:Degraded SMARCA2 in a dose-dependent manner.
Showed minimal degradation of SMARCA4 even at the highest tested concentration.
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Cell Line:SK-Mel-5 SMARCA4 mutant melanoma cells
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM
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Incubation Time:24 h
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Result:Potently degraded SMARCA2 with a DC50 of 81.1 nM and a Dmax of 87%.
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Cell Line:H838 SMARCA4 mutant lung cancer cells
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Concentration:0.001, 0.01, 0.1, 1, 10, 100, 1000 nM
-
Incubation Time:24 h
-
Result:Potently degraded SMARCA2 with a DC50 of 76.2 nM and a Dmax of 89%.
-
Cell Line:H1792 SMARCA4 wild-type cells
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Concentration:0.1, 1, 10,100, 1000, 10000 nM
-
Incubation Time:24 h
-
Result:Degraded PBRM1 in a dose-dependent manner, with a DC50 of ~100 nM and a Dmax of 62% at 1 μM.
-
Cell Line:H1792 and SK-Mel-28 SMARCA2/4 wild-type cancer cell lines
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Concentration:0.0001, 0.001, 0.01, 0.1, 1 μM
-
Incubation Time:7 days
-
Result:Showed no cell growth inhibition activity at concentrations up to 1 μM, with a GI50 > 1000 nM and Imax of 0% in both cell lines.
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Cell Line:H838 and SK-Mel-5 SMARCA4 deficient cancer cell lines
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Concentration:0.0001, 0.001, 0.01, 0.1, 1 μM
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Incubation Time:7 days
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Result:Inhibited cell growth in a dose-dependent manner: in H838 cells, GI50 = 142 nM with an Imax of 79%; in SK-Mel-5 cells, GI50 = 22.3 nM with an Imax of 93%.
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Cell Line:H1792 cells
-
Concentration:0.1, 1, 10, 100, 1000 nM
-
Incubation Time:24 h
-
Result:Reduced PBRM1 protein levels.
Chemical Information
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CAS No. 3033586-04-5
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Molecular Weight 986.70
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Formula C56H68ClN7O5S
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SMILES
C[C@H](NC([C@@H]1C[C@H](CN1C([C@@H](NC([C@@H]2CC[C@H](CC2)CN3CCC(CC3)C4=CC(N5C6=C7C(Cl)=CC=C6)=C(C=C4)C8(CCCCC8)C5=NC7=O)=O)C(C)(C)C)=O)O)=O)C9=CC=C(C=C9)C%10=C(C)N=CS%10
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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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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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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
[1]. Yang L, et al. Discovery of SMD-3236: A Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers. Journal of medicinal chemistry. 2025 Jan 23;68(2):1155-1178. [Content Brief]
[2]. Leng L, et al. Discovery of High-Affinity SMARCA2/4 Bromodomain Ligands and Development of Potent and Exceptionally Selective SMARCA2 PROTAC Degraders. Journal of medicinal chemistry. 2025 Jan 23;68(2):1113-1133. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)