Tumor microenvironment is now getting much attention as tumor therapeutic targets. We have been studying the tumor-stromal cell interactions and found new candidates for antitumor drugs. We have then reported various compounds that inhibit tumor growth through the modulation of the tumor-stromal cell interactions (Cancer Res 66, 4419, 2006; Int J Cancer 126, 810, 2010; J Antibiot 63, 319, 2010). In this report we have focused on the binding of cells to ligands.

Interaction between the receptor for advanced glycation end-product (RAGE) and amphoterin plays an important role in tumor growth and metastasis. Because the abrogation of the interaction results in the inhibition of the tumor growth and metastasis, we designed a screening system for an inhibitor of the interaction between RAGE and amphoterin. In the course of our screening of the inhibitor, we isolated a novel natural compound NBRI17671 (1) from the fermentation broth of Acremonium sp. CR17671. We also modified 1 into more active NBRI17671al (2). While 1 at 50 μg/ml weakly inhibited binding of various cells to amphoterin, 2 at 50 μg/ml inhibited it more than 50% of control. Compound 2 effectively inhibited the tumor growth of glioma and lung tumor xenografts in mice at 25 mg/kg. Furthermore, 2 was found to downregulate MAPK activity in the tumor cells. Collaborator: Meiji Seika Pharma.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B169.