Signal transducer and activator of transcription (STAT) 3, a member of a family 
of DNA-binding molecules, is a potential target in the treatment of cancer. The 
highly phosphorylated STAT3 in cancer cells contributes to numerous 
physiological and oncogenic signaling pathways. Furthermore, a significant 
association between STAT3 signaling and glioblastoma multiforme stem-like cell 
(GBM-SC) development and maintenance has been demonstrated in recent studies. 
Previously, we reported a novel small molecule inhibitor of STAT3 dimerization, 
STX-0119, as a cancer therapeutic. In the present study, we focused on cancer 
stem-like cells derived from recurrent GBM patients and investigated the 
efficacy of STX-0119. Three GBM stem cell lines showed many stem cell markers 
such as CD133, EGFR, Nanog, Olig2, nestin and Yamanaka factors (c-myc, KLF4, 
Oct3/4 and SOX2) compared with parental cell lines. These cell lines also formed 
tumors in vivo and had similar histological to surgically resected tumors. STAT3 
phosphorylation was activated more in the GBM-SC lines than serum-derived GB 
cell lines. The growth inhibitory effect of STX-0119 on GBM-SCs was moderate 
(IC50 15-44 µM) and stronger compared to that of WP1066 in two cell lines. On 
the other hand, the effect of temozolomide was weak in all the cell lines (IC50 
53-226 µM). Notably, STX-0119 demonstrated strong inhibition of the expression 
of STAT3 target genes (c-myc, survivin, cyclin D1, HIF-1α and VEGF) and stem 
cell-associated genes (CD44, Nanog, nestin and CD133) as well as the induction 
of apoptosis in one stem-like cell line. Interestingly, VEGFR2 mRNA was also 
remarkably inhibited by STX-0119. In a model using transplantable stem-like cell 
lines in vivo GB-SCC010 and 026, STX-0119 inhibited the growth of GBM-SCs at 80 
mg/kg. STX-0119, an inhibitor of STAT3, may serve as a novel therapeutic 
compound against GBM-SCs even in temozolomide-resistant GBM patients and has the 
potential for GBM-SC-specific therapeutics in combination with temozolomide plus 
radiation therapy.