62484-40-6Relevant academic research and scientific papers
Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer
Shirai, Fumiyuki,Mizutani, Anna,Yashiroda, Yoko,Tsumura, Takeshi,Kano, Yuko,Muramatsu, Yukiko,Chikada, Tsubasa,Yuki, Hitomi,Niwa, Hideaki,Sato, Shin,Washizuka, Kenichi,Koda, Yasuko,Mazaki, Yui,Jang, Myung-Kyu,Yoshida, Haruka,Nagamori, Akiko,Okue, Masayuki,Watanabe, Takashi,Kitamura, Kouichi,Shitara, Eiki,Honma, Teruki,Umehara, Takashi,Shirouzu, Mikako,Fukami, Takehiro,Seimiya, Hiroyuki,Yoshida, Minoru,Koyama, Hiroo
supporting information, p. 4183 - 4204 (2020/05/20)
Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase inhibitor. Herein we describe the optimization process of RK-287107 leading to RK-582, which exhibits a markedly improved robust tumor growth inhibition in a COLO-320DM mouse xenograft model when orally administered. In addition to the dose-dependent elevation and attenuation of the levels of biomarkers AXIN2 and β-catenin, respectively, results of the TCF reporter and cell proliferation studies on COLO-320DM are discussed.
HETEROCYCLIC COMPOUNDS AS ANTIBIOTIC POTENTIATORS
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Paragraph 0986, (2016/07/05)
The invention relates to heterocyclic compounds and their use as antibiotics and/or as antibiotic potentiators. The compounds may act as colistin potentiators and SOS inhibitors.
