Thursday, September 20, 2012
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Bromodomain containing 4 (BRD4)
Mouse and cell culture
studies suggest inhibiting BRD4 can modulate the T cell response to help
treat inflammatory diseases. In naïve T cells cultured under T helper type 1
(Th1) cell-promoting conditions, I-BET-762, an inhibitor of bromodomain
and extra terminal domain (BET) bromodomains including BRD4, upregulated
expression of anti-inflammatory cytokines and downregulated expression of
proinflammatory cytokines. In a model of autoreactive Th1 cell-induced
experimental autoimmune encephalomyelitis (EAE), pretreatment of Th1 cells
with I-BET-762 decreased disease severity compared with pretreatment using an
inactive control compound (p<0.0001). Next
steps include testing I-BET-762 in preclinical models of immune-mediated
diseases such as asthma.
I-BET-762 is a BET bromodomain inhibitor from GlaxoSmithKline
plc, which had researchers involved in the study.
Therapeutics Inc. has BET bromodomain inhibitors in
preclinical development for cancer.
Pharmaceuticals Inc. has BET bromodomain inhibitors in
preclinical development for cancer and immunological indications.
Published online Sept. 20, 2012
Patent status undisclosed;
unavailable for licensing
H.S. et al. Proc. Natl. Acad. Sci. USA; published online Aug. 21,
Contact: Anjana Rao, La Jolla Institute for Allergy &
Immunology, La Jolla, Calif.
Contact: Hozefa S. Bandukwala,
same affiliation as above
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