SD-965
SD-965 is a selective STAT3 PROTAC degrader with a DC50 of 0.14 μM. SD-965 promotes the ubiquitination and degradation of STAT3. SD-965 induces rapid, complete and persistent depletion of STAT3 protein. SD-965 induces tumor regression in mouse xenograft models of leukemia and lymphoma.
(Pink: STAT3 Target protein ligand; Blue: Cereblon ligand (HY-W1009348); Black: linker (HY-W017522)).
For research use only. We do not sell to patients.
- CAS No.: 3054394-56-5
- Formula: C56H65N10O17PS
- Molecular Weight:1213.21
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
STAT3 0.14 μM (DC50) |
In Vitro
SD-965 (up to 5 μM; 24 h) potently degrades STAT3 in the STAT3 HiBiT assay with a DC50 of 0.14 μM and 85% maximal degradation after 24 h incubation[1].
SD-965 potently inhibits the growth of MOLM-16 leukemia cells (IC50 = 1.3 nM) and SU-DHL-1 lymphoma cells (IC50 = 260 nM)[1].
SD-965 (3.2-2000 nM; 14 h) selectively degrades STAT3 with >90% maximal degradation in human PBMCs after 14 h incubation, with no significant effect on other STAT family proteins up to 2 μM[1].
SD-965 exhibits excellent microsomal and plasma stability in mouse, rat, dog, monkey, and human, with a half-life of >120 min in all tested matrices[1].
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:SU-DHL-1 human anaplastic large cell lymphoma cells
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Concentration:3.2-2000 nM
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Incubation Time:14 h
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Result:Degraded STAT3 with a DC50 of 80 nM and a Dₘₐₓ of >90%.
Showed no obvious effect on STAT1 or STAT6, modestly reduced STAT2 and STAT5 at 2 μM, and increased STAT4 levels in a dose-dependent manner.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SU-DHL-1 lymphoma xenograft mouse model[1]
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Dosage:25-50 mg/kg
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Administration:i.v.; once weekly; for 3-4 consecutive weeks
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Result:Induced a maximum tumor regression by 58% at 25 mg/kg.
Reduced the tumor volume by 52% on day 5 after the first dose and by 96% on day 16, with 60% of mice without palpable tumors (50 mg/kg).
Chemical Information
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CAS No. 3054394-56-5
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Molecular Weight 1213.21
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Formula C56H65N10O17PS
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SMILES
O=C(P(O)(O)=O)C1=CC2=C(NC(C(N[C@H]3CN(C(CCCCC(N4C[C@@]5([H])N(C6=C(OC5)C7=C(C(N([C@@H](CC8)C(NC8=O)=O)C7)=O)C=C6)CC4)=O)=O)CC[C@](CC[C@H]9C(N[C@@H](CCC(N)=O)COC%10=CC=CC(S(=O)(C)=O)=C%10)=O)([H])N9C3=O)=O)=C2)C=C1
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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)