17759-30-7Relevant articles and documents
Pyridopyrimidinone derivatives as potent and selective c-jun N-terminal kinase (JNK) inhibitors
Zheng, Ke,Park, Chul Min,Iqbal, Sarah,Hernandez, Pamela,Park, Hajeung,Lograsso, Philip V.,Feng, Yangbo
, p. 413 - 418 (2015)
A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure-activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 μM), had high potency in functional cell based assays, and had high stability in human liver microsome (t1/2 = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 ?. These structures elucidated the binding mode (Type-I binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.
Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma
Liu, Haibo,Niu, Deqiang,Tham Sjin, Robert Tjin,Dubrovskiy, Alex,Zhu, Zhendong,Mcdonald, Joseph J.,Fahnoe, Kelly,Wang, Zhigang,Munson, Mark,Scholte, Andrew,Barrague, Matthieu,Fitzgerald, Maria,Liu, Jinyu,Kothe, Michael,Sun, Fangxian,Murtie, Joshua,Ge, Jie,Rocnik, Jennifer,Harvey, Darren,Ospina, Beatriz,Perron, Keli,Zheng, Gang,Shehu, Elvis,D'Agostino, Laura Akullian
, p. 1899 - 1904 (2020)
Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer and is one of the most common forms of cancer worldwide. Aberrant signaling of the FGF19-FGFR4 pathway leads to HCC in mice and is hypothesized to be a driver in FGF19 amplifie
PROTEIN KINASE INHIBITORS AND USES THEREOF FOR THE TREATMENT OF DISEASES AND CONDITIONS
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, (2020/11/30)
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2) and/or receptor interacting kinase 3 (RIPK3). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 or RIPK3 could provide therapeutic benefit. Compounds that function as RIPK3 inhibitors provide therapeutic benefit in the treatment of inflammatory and degenerative conditions.
