Discovery of Novel Spiroindoline Derivatives as Selective Tankyrase Inhibitors was written by Shirai, Fumiyuki;Tsumura, Takeshi;Yashiroda, Yoko;Yuki, Hitomi;Niwa, Hideaki;Sato, Shin;Chikada, Tsubasa;Koda, Yasuko;Washizuka, Kenichi;Yoshimoto, Nobuko;Abe, Masako;Onuki, Tetsuo;Mazaki, Yui;Hirama, Chizuko;Fukami, Takehiro;Watanabe, Hirofumi;Honma, Teruki;Umehara, Takashi;Shirouzu, Mikako;Okue, Masayuki;Kano, Yuko;Watanabe, Takashi;Kitamura, Kouichi;Shitara, Eiki;Muramatsu, Yukiko;Yoshida, Haruka;Mizutani, Anna;Seimiya, Hiroyuki;Yoshida, Minoru;Koyama, Hiroo. And the article was included in Journal of Medicinal Chemistry in 2019.Related Products of 58333-75-8 This article mentions the following:
The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ribose) polymerase catalytic activity of the tankyrases (TNKS/TNKS2) has been reported to reduce the Wnt/β-catenin signal by preventing poly ADP-ribosylation dependent degradation of AXIN, a neg. regulator of Wnt/β-catenin signaling. With the goal of investigating the effects of tankyrase and Wnt pathway inhibition on tumor growth, we set out to find small mol. inhibitors of TNKS/TNKS2 with suitable drug-like properties. Starting from 1a(I), a high-throughput screening hit, the spiroindoline derivative 40c(II) (RK-287107) was discovered as a potent TNKS/TNKS2 inhibitor with >7,000-fold selectivity against the PARP1 enzyme, which inhibits WNT-responsive TCF reporter activity and proliferation of human colorectal cancer cell line COLO-320DM. II also demonstrated dose-dependent tumor growth inhibition in a mouse xenograft model. These observations suggest that II is a promising lead compound for the development of novel tankyrase inhibitors as anticancer agents. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8Related Products of 58333-75-8).
4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Related Products of 58333-75-8
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem