E-viri
Recenzirano
Odprti dostop
-
Ramurthy, Savithri; Taft, Benjamin R; Aversa, Robert J; Barsanti, Paul A; Burger, Matthew T; Lou, Yan; Nishiguchi, Gisele A; Rico, Alice; Setti, Lina; Smith, Aaron; Subramanian, Sharadha; Tamez, Victoriano; Tanner, Huw; Wan, Lifeng; Hu, Cheng; Appleton, Brent A; Mamo, Mulugeta; Tandeske, Laura; Tellew, John E; Huang, Shenlin; Yue, Qin; Chaudhary, Apurva; Tian, Hung; Iyer, Raman; Hassan, A. Quamrul; Mathews Griner, Lesley A; La Bonte, Laura R; Cooke, Vesselina G; Van Abbema, Anne; Merritt, Hanne; Gampa, Kalyani; Feng, Fei; Yuan, Jing; Mishina, Yuji; Wang, Yingyun; Haling, Jacob R; Vaziri, Sepideh; Hekmat-Nejad, Mohammad; Polyakov, Valery; Zang, Richard; Sethuraman, Vijay; Amiri, Payman; Singh, Mallika; Sellers, William R; Lees, Emma; Shao, Wenlin; Dillon, Michael P; Stuart, Darrin D
Journal of medicinal chemistry, 03/2020, Letnik: 63, Številka: 5Journal Article
Direct pharmacological inhibition of RAS has remained elusive, and efforts to target CRAF have been challenging due to the complex nature of RAF signaling, downstream of activated RAS, and the poor overall kinase selectivity of putative RAF inhibitors. Herein, we describe 15 (LXH254, Aversa, R.; et al. Int. Patent WO2014151616A1, 2014), a selective B/C RAF inhibitor, which was developed by focusing on drug-like properties and selectivity. Our previous tool compound, 3 (RAF709; Nishiguchi, G. A.; et al. J. Med. Chem. 2017, 60, 4969), was potent, selective, efficacious, and well tolerated in preclinical models, but the high human intrinsic clearance precluded further development and prompted further investigation of close analogues. A structure-based approach led to a pyridine series with an alcohol side chain that could interact with the DFG loop and significantly improved cell potency. Further mitigation of human intrinsic clearance and time-dependent inhibition led to the discovery of 15. Due to its excellent properties, it was progressed through toxicology studies and is being tested in phase 1 clinical trials.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.