当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development.

Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development.

Abstract：

:The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small molecule inhibitor selective for ERK kinase activity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Blake JF,Burkard M,Chan J,Chen H,Chou KJ,Diaz D,Dudley DA,Gaudino JJ,Gould SE,Grina J,Hunsaker T,Liu L,Martinson M,Moreno D,Mueller L,Orr C,Pacheco P,Qin A,Rasor K,Ren L,Robarge K,Shahidi-Latham S,Stults J,S

doi

10.1021/acs.jmedchem.6b00389

subject

Has Abstract

pub_date

2016-06-23 00:00:00

pages

5650-60

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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