21109-25-1Relevant articles and documents
Isobrassinin and its analogues: Novel types of antiproliferative agents
Csomos, Peter,Zupko, Istvan,Rethy, Borbala,Fodor, Lajos,Falkay, George,Bernath, Gabor
, p. 6273 - 6276 (2006)
Isobrassinin (2-(S-methyldithiocarbamoylaminomethyl)indole (7a), a regioisomer of the cruciferous phytoalexin brassinin (1), exerted marked antiproliferative effects on the HeLa, A431 and MCF7 cell lines (>78.6% inhibition at 30 μM). For structure-activity relationships, further analogues were synthesized. The highest cytotoxic effect was displayed by 2-phenylimino-1,3-thiazino[5,6-b]indole (10) (10 μM, 76.8%-HeLa and 46.3%-MCF7). The effect of the natural phytoalexin brassinin was also determined.
Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)
Zhou, Han-Jie,Wang, Jinhai,Yao, Bing,Wong, Steve,Djakovic, Stevan,Kumar, Brajesh,Rice, Julie,Valle, Eduardo,Soriano, Ferdie,Menon, Mary-Kamala,Madriaga, Antonett,Kiss Von Soly, Szerenke,Kumar, Abhinav,Parlati, Francesco,Yakes, F. Michael,Shawver, Laura,Le Moigne, Ronan,Anderson, Daniel J.,Rolfe, Mark,Wustrow, David
, p. 9480 - 9497 (2016/01/12)
The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.
Application of alkoxide in catalytic transfer hydrogenation of unsaturated nitrogen compounds
Chen, Xinzhi,Zhou, Shaodong,Chen, Yuehan,Dong, Zehan,Gao, Yeyu,Qian, Chao,He, Chaohong
, p. 2255 - 2269 (2013/02/23)
Alcoholate was utilized in catalytic transfer hydrogenation of unsaturated nitrogen compounds. In the reduction of nitro compounds, oximes and imines, alkoxide was used as the promoter, with alcohol as the hydrogen source, while in the reduction of nitriles, alkoxide was used as the hydrogen source. Springer Science+Business Media B.V. 2012.
