当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity.

Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity.

Abstract：

:Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

May-Dracka TL,Arduini R,Bertolotti-Ciarlet A,Bhisetti G,Brickelmaier M,Cahir-McFarland E,Enyedy I,Fontenot JD,Hesson T,Little K,Lyssikatos J,Marcotte D,McKee T,Murugan P,Patterson T,Peng H,Rushe M,Silvian L,Spilker K

doi

10.1016/j.bmcl.2018.03.032

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1964-1971

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30221-X

journal_volume

28

pub_type

杂志文章

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