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^[1][2]. 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 Stat3^Tyr705, 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]. In Vivo:NSC-368262 (200 mg/kg; i.p.; 5 days per week; 8 weeks) significantly inhibits the growth of MDA-MB-468 human breast cancer xenografts in athymic nude mice^[1].
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].