NSC-368262
NSC-368262 is a STAT3 inhibitor. NSC-368262 selectively alkylates and covalently modifies STAT3 Cys468 at the DNA-binding interface of STAT3, blocks the DNA-binding activity of STAT3, and inhibits the phosphorylation of STAT3. NSC-368262 blocks the accumulation of activated STAT3 in the nucleus of cancer cells, induces PARP cleavage and apoptosis in cells, and inhibits tumor growth in mouse models. NSC-368262 can be used in research related to breast cancer and cervical cancer.
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- No. CAS: 299421-08-2
- Fòrmula: C22H22N2O6
- Peso molecular:410.43
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
STAT3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| SK-MEL-5 | IC50 |
10 μM
Compound: 81; C48
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Inhibition of recombinant STAT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA binding activity with SK-MEL-5 nuclear extract incubated for 30 mins by electrophoretic mobility shift assay
Inhibition of recombinant STAT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in DNA binding activity with SK-MEL-5 nuclear extract incubated for 30 mins by electrophoretic mobility shift assay
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[PMID: 31810784] |
In Vitro
NSC-368262 (C48) (0-500 μM; 30 min) selectively blocks the DNA-binding activity of activated Stat3 homodimers and Stat1/Stat3 heterodimers in nuclear extracts of IFN-γ-stimulated human melanoma Sk-Mel-5 cells, with corresponding IC50 values of 10-50 μM and 50-100 μM[1].
NSC-368262 (0-300 μM; 30 min) inhibits the DNA-binding activity of Stat3 in nuclear extracts of Sk-Mel-5 human melanoma cells only when it interacts with the Stat3 protein prior to Stat3 binding to DNA[1].
NSC-368262 (0-600 μM; 30 min) inhibits the DNA-binding activity of Stat3 via modifying Cys468, leading to alkylation modification of Stat3[1].
NSC-368262 (40 μM; 2 h) completely inhibits Oncostatin M-induced nuclear accumulation of Stat3-YFP in serum-starved MEF-Stat3-YFP mouse embryonic fibroblasts[1].
NSC-368262 (1-20 μM; 2 h) dose-dependently inhibits Stat3-mediated transcriptional activity in HeLa-Stat3-Luc human cervical cancer cells, with an IC50 of 3-10 μM[1].
NSC-368262 (1-20 μM; 48 h) induces apoptosis in human breast cancer cells MDA-MB-468 and MDA-MB-231 with constitutive Stat3 activity, with an IC50 of 10-20 μM after 48 h of treatment, but fails to induce apoptosis in human prostate cancer cells LNCaP lacking constitutive Stat3 activity[1].
NSC-368262 (1-20 μM; 48 h) inhibits the phosphorylation of Stat3Tyr705, blocks the expression of Mcl-1, and induces PARP cleavage (apoptosis) in human breast cancer MDA-MB-468 cells after 48 h of treatment; at a concentration of 20 μM, it completely inhibits the phosphorylation of Stat3 and the expression of Mcl-1[1].
NSC-368262 (0-50 μM) potently and selectively inhibits the DNA-binding activity of STAT3 in vitro with an IC50 of 10 μM, and suppresses STAT3-mediated transcriptional activity in HeLa cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-468 human breast cancer cells, MDA-MB-231 human breast cancer cells, LNCaP human prostate cancer cells
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Concentration:1, 3, 10, 20 μM
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Incubation Time:48 h
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Result:Induced apoptosis in MDA-MB-468 and MDA-MB-231 cells with an IC50 of 10-20 μM.
Did not induce apoptosis in LNCaP cells.
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Cell Line:MDA-MB-468 human breast cancer cells
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Concentration:1, 3, 10, 20 μM
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Incubation Time:48 h
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Result:Reduced Stat3 Tyr705 phosphorylation at 10 μM.
Completely inhibited Stat3 Tyr705 phosphorylation at 20 μM.
Fully blocked expression of pro-survival Stat3 target gene Mcl-1 at 20 μM.
Induced cleavage of PARP (a marker of apoptosis) at 20 μM.
Did not significantly inhibit activation state of p44/p42 MAP kinases even at 20 μM.
Parmacokinetics
In Vivo
NSC-368262 (100-200 mg/kg; i.p.; 5 days per week; 2 weeks) significantly inhibits the growth of C3L5 mouse breast cancer xenografts in vivo in syngeneic mouse models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:athymic nude mice (6-week-old)[1]
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Dosage:200 mg/kg
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Administration:i.p.; once daily, 5 days per week; 8 weeks
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Result:Inhibited tumor growth significantly compared to vehicle-treated controls.
Caused no lethal toxicity or greater than 10% body weight loss.
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Animal Model:C3H/HeJ mice (female, 7-9-week-old)[1]
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Dosage:100 mg/kg; 200 mg/kg
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Administration:i.p.; once daily, 5 days per week; 2 cycles
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Result:Inhibited tumor growth significantly compared to vehicle-treated controls at 200 mg/kg.
Showed no specific quantitative outcome data for the 100 mg/kg dose.
Chemical Information
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No. CAS 299421-08-2
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Peso molecular 410.43
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Fòrmula C22H22N2O6
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SMILES
OC=1C=C2OCOC2=CC1C(NC3=NC=CC=C3)C4=CC(OC)=C(OC)C(OC)=C4
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Buettner R, et al. Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development. ACS Chem Biol. 2011;6(5):432-443. [Content Brief]
[2]. Huang Q, et al. Revisiting signal transducer and activator of transcription 3 (STAT3) as an anticancer target and its inhibitor discovery: Where are we and where should we go?. Eur J Med Chem. 2020;187:111922. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NSC-368262 Related Classifications
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