Discovery of IDO1 and DNA dual targeting antitumor agents. Issue 47 (27th November 2017)

• Record Type: Journal Article
• Authors: Fang, Kun; Wu, Shanchao; Dong, Guoqiang; Wu, Ying; Chen, Shuqiang; Liu, Jianhe; Wang, Wei; Sheng, Chunquan
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 47(2017)
• Page Start: 9992
• Page End: 9995
• Publication Date: 2017-11-27
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02529g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2, 3-dioxygenase 1 (IDO1) represents a promising target. Abstract : The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2, 3-dioxygenase 1 (IDO1) represents a promising target. Inspired by the synergistic effects between IDO1 inhibitors and traditional antitumor chemotherapeutics, the first orally active dual IDO1 and DNA targeting agents were designed by the pharmacophore fusion strategy. The bifunctional hybrids exhibited enhanced IDO1 enzyme inhibitory activity and in vitro cytotoxicity as compared to IDO1 inhibitor 1-methyl-tryptophan and DNA alkylating agent melphalan. In a murine LLC tumor model, the dual targeting agents demonstrated excellent antitumor efficacy, highlighting the advantages of this novel design strategy to improve the efficacy of small molecule cancer immunotherapy.