In cytotoxic conditions such as hypoxia, nutrient deprivation and low pH, unfolded proteins accumulate in cells, leading to ER stress. Poorly vascularized solid-tumor cells are considered to adapt to ER stress by activating a transcription factor XBP1, resulting in tumor survival. Therefore, inhibitors of XBP1 activation would be a new type of anticancer drugs. To screen for inhibitors of ER stress-induced XBP1 activation, we established a screening system (Fig. 1), and isolated novel triene-ansamycin group compounds trierixin and quinotrierixin from culture broths of Streptomyces sp. AC654 and Streptomyces sp. PAE37, respectively (Fig. 3). The planar structures of trierixin and quinotrierixin were elucidated on the basis of the spectroscopical properties (Fig. 2). Trierixin inhibited ER stress-induced XBP1 activation and cell growth of HeLa cells with IC_<50> of 28nM and 10nM, respectively. Quinotrierixin also showed both inhibitory activities with the same dose range. Therefore, we proposed a hypothesis that triene-ansamycin group compounds inhibited tumor cell growth via inhibition of XBP1 activation. To confirm this possibility, we isolated six additional triene-ansamycin group compounds (including three novel compounds) from the culture broth of Streptomyces sp. PAE37 by referring to the characteristic UV spectra (λ_<max> 260, 270 and 280nm), and prepared four derivatives by chemical reactions on the natural products (Fig. 3, Fig. 4). Using these compounds, we performed SAR study of triene-ansamycin group compounds. As a result, there was high correlation between inhibitory effects of triene-ansamycin group compounds against XBP1 activation and those against tumor cell growth (Fig. 5).