76360-82-2Relevant articles and documents
Development of radioiodinated pyrimidinopyridone derivatives as targeted imaging probes of activated p38α for single photon emission computed tomography
Hashimoto, Tomoyuki,Kondo, Naoya,Hirata, Masahiko,Temma, Takashi
, p. 1293 - 1304 (2021/08/23)
Objective: p38α, a member of the mitogen-activated protein kinase superfamily, is ubiquitously expressed in a variety of mammalian cells. Activated p38α induces inflammatory responses to external stimuli, suggesting that non-invasive detection of activate
Design of pyrido[2,3-d]pyrimidin-7-one inhibitors of receptor interacting protein kinase-2 (RIPK2) and nucleotide-binding oligomerization domain (NOD) cell signaling
Nikhar, Sameer,Siokas, Ioannis,Schlicher, Lisa,Lee, Seungheon,Gyrd-Hansen, Mads,Degterev, Alexei,Cuny, Gregory D.
, (2021/02/22)
Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain (NOD) cell signaling, a pathway implicated in numerous chronic inflammatory conditions. Herein, a pyrido[
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
supporting information, p. 1899 - 1904 (2020/11/09)
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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Paragraph 0106; 0109; 0110, (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.
FGFR4 kinase inhibitor, preparation method and uses thereof
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Paragraph 0203-0204; 0206-0207, (2020/04/17)
The present invention relates to a compound represented by a formula (I), or a pharmaceutically acceptable salt, a solvate, a polymorph or an isomer thereof, and uses in preparation of drugs for treatment of FGFR4 mediated diseases.
PYRIDO[2,3-D]PYRIMIDIN-7ONES AND RELATED COMPOUNDS AS INHIBITORS OF PROTEIN KINASES
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Paragraph 0049-0050; 0006; 0007, (2018/12/13)
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.
Discovery of 2-((3-Acrylamido-4-methylphenyl)amino)-N-(2-methyl-5-(3,4,5-trimethoxybenzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-BMX-078) as a Highly Potent and Selective Type II Irreversible Bone Marrow Kinase in the X Chromosome (BMX) Kinase Inhibitor
Liang, Xiaofei,Lv, Fengchao,Wang, Beilei,Yu, Kailin,Wu, Hong,Qi, Ziping,Jiang, Zongru,Chen, Cheng,Wang, Aoli,Miao, Weili,Wang, Wenchao,Hu, Zhenquan,Liu, Juan,Liu, Xiaochuan,Zhao, Zheng,Wang, Li,Zhang, Shanchuan,Ye, Zi,Wang, Chu,Ren, Tao,Wang, Yinsheng,Liu, Qingsong,Liu, Jing
, p. 1793 - 1816 (2017/03/17)
BMX is a member of TEC family nonreceptor tyrosine kinase and is involved in a variety of critical physiological and pathological processes. Through combination of irreversible inhibitor design and type II inhibitor design approaches, we have discovered a highly selective and potent type II irreversible BMX kinase inhibitor compound 41 (CHMFL-BMX-078), which exhibited an IC50 of 11 nM by formation of a covalent bond with cysteine 496 residue in the DFG-out inactive conformation of BMX. It displayed a high selectivity profile (S score(1) = 0.01) against the 468 kinases/mutants in the KINOMEscan evaluation and achieved at least 40-fold selectivity over BTK kinase. Given the fact that BMX mediated signaling pathway is still not fully understood, compound 41 would serve as a useful pharmacological tool to elucidate the detailed mechanism of BMX mediated signaling pathways.
Inhibitors of the fibroblast growth factor receptor
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Page/Page column 48, (2017/08/01)
Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of FGFR-4.
Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia
Liang, Xiaofei,Liu, Xiaochuan,Wang, Beilei,Zou, Fengming,Wang, Aoli,Qi, Shuang,Chen, Cheng,Zhao, Zheng,Wang, Wenchao,Qi, Ziping,Lv, Fengchao,Hu, Zhenquan,Wang, Li,Zhang, Shanchun,Liu, Qingsong,Liu, Jing
, p. 1984 - 2004 (2016/03/22)
Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM), and MEG-01 (GI50 = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.
PREPARATION AND USE OF NOVEL PROTEIN KINASE INHIBITORS
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Paragraph 151, (2016/11/14)
The invention provides novel compounds and methods of using such compounds to treat or prevent cancer.
