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Inflammatory disease; asthma

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.
Tensha Therapeutics Inc. has BET bromodomain inhibitors in preclinical development for cancer.
Constellation Pharmaceuticals Inc. has BET bromodomain inhibitors in preclinical development for cancer and immunological indications.

SciBX 5(37); doi:10.1038/scibx.2012.983
Published online Sept. 20, 2012

Patent status undisclosed; unavailable for licensing

Bandukwala, H.S. et al. Proc. Natl. Acad. Sci. USA; published online Aug. 21, 2012;
Contact: Anjana Rao, La Jolla Institute for Allergy & Immunology, La Jolla, Calif.
Contact: Hozefa S. Bandukwala,
same affiliation as above