الفهرس 
Novel diaryl urea based compounds
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Abstract
Breast cancer is the most common cancer diagnosed in women. Tamoxifen (TAM) is the gold standard in therapy of estrogen receptor positive breast cancer (ER+ BC), however its efficacy is challenged by acquired resistance. Angiogenesis plays fundamental roles in TAM resistance where VEGFR-2 is a key player in this process. Thus, targeting of VEGFR-2 signaling pathway has been an attractive approach for BC therapy. In this study, we synthesized a new thieno[2,3-d]pyrimidine based urea derivative KM6, which exhibited potential antitumor activity in both TAM-sensitive MCF7 and TAM-resistant LCC2 BC cells. In addition to its antiangiogenic properties, KM6 retained the sensitivity of LCC2 via modulation of key proteins and enzymes of apoptosis and cell death (caspases 3,8,9, survivin, P53, BAX, BCL-2, LDH) and ROS. Moreover, KM6 modulated vital biological markers of inflammation (PGE2, COX2, IL-1Ý and IL6) and metastasis (MMP-2 and MMP-9). Thus, KM6 is a promising compound for ER+ and TAM-resistant BC with polypharmacological properties