BD750

BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC50 values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively[1][2].

Signaling Pathways >> Stem Cell/Wnt >> STAT

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> JAK

Signaling Pathways >> Epigenetics >> JAK

Signaling Pathways >> Stem Cell/Wnt >> JAK

Signaling Pathways >> JAK/STAT Signaling >> STAT

Research Areas >> Inflammation/Immunology

JAK3

STAT5

BD750 inhibits human T cell proliferation stimulated either by anti-CD3/anti-CD28 mAbs or by alloantigen in a dose-dependent manner with IC50 values of 1.1 ± 0.2 μM and 1.3 ± 0.2 μM respectively[1]. BD750 also inhibits ConA, PMA/ionomycine or alloantigen-induced mouse T cell proliferation and PHA or PMA/ionomycine-induced human T cell proliferation[1]. BD750 (5 or 20 μM) inhibits the LPS-induced JAK-STAT5 signaling in DC[2]. Western Blot Analysis[2] Cell Line: Purified immature DCs. Concentration: 1, 5 or 20 μM. Incubation Time: 12 h. Result: Had fewer small dendrites and smaller clusters than typical mDCs (5 or 20 μM). At a higher dose significantly reduced the levels of LPS-stimulated IL-6, IL-12, TNF-α, IL-1β and IL-23 production by DCs.

BD750 can induce tolerogenic dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice[2]. Animal Model: Female C57BL/6 mice (10 wks old, 19-21 g)[2]. Dosage: 20 μM. Administration: IV, treated DC on d 7, 11 and 15 post the first PTX injection (dpi 7, 11 and 15). Result: Significantly reduced the frequency of Th1 and Th17 cells and increased the percentage of Tregs compared with mice receiving PBS.

[1]. Y Liu, et al. BD750, a benzothiazole derivative, inhibits T cell proliferation by affecting the JAK3/STAT5 signalling pathway. Br J Pharmacol. 2013 Feb;168(3):632-43.

[2]. Yan Zhou, et al. Tolerogenic dendritic cells induced by BD750 ameliorate proinflammatory T cell responses and experimental autoimmune encephalitis in mice. Mol Med. 2017 Oct;23:204-214.