BC12

BC12 is a barbituric acid derivative and a phosphodiesterase 7 (PDE7) inhibitor, with an IC₅₀ of 0.77 μM against human targets. BC12 inhibits the enzymatic activity of PDE7, but this activity is not the driver of its immunomodulatory effects on T lymphocytes. BC12 blocks the upregulation of IL-2 transcription in activated T cells. BC12 modulates the transcriptional response of T cells upon stimulation, exerting anti-inflammatory and pro-stress effects. BC12 inhibits the proliferation of primary mouse T cells and the IL-2 secretion of human peripheral blood T lymphocytes. BC12 exerts immunosuppressive and immunomodulatory effects on T lymphocyte function. BC12 can be used in research related to T lymphocyte-mediated diseases^[1]. In Vitro:BC12 potently and selectively inhibits purified human PDE7A with an IC₅₀ of 0.77 μM, while displaying minimal activity against other PDE family enzymes at 10 μM^[1].
BC12 (10 μM) inhibits greater than 95% of IL-2 secretion in PHA/PMA-stimulated Jurkat T cells by blocking IL-2 transcription, with no significant reduction in cell viability^[1].
BC12 (10 μM; 24-48 h) potently inhibits IL-2 secretion in primary mouse splenic T cells and human primary peripheral blood T cells stimulated with PMA/ionomycin and anti-CD3/anti-CD28^[1].
BC12 (10 μM; 48 h) potently inhibits proliferation of PMA/ionomycin-stimulated primary murine splenic T cells by blocking entry into S + G2/M phase of the cell cycle^[1].
BC12 (10 μM; 24 h) significantly reduces the increased surface expression of CD44 and CD69 activation markers in PMA/ionomycin-stimulated primary murine splenic T cells after 24 h^[1].
BC12 (10 μM) modulates global gene expression in Jurkat T cells, reducing the transcriptional induction of key T cell function and immune response genes upon PMA/PHA stimulation and inducing a stress response in unstimulated cells^[1].
BC12 (10 μM; 20 min pre-incubation, followed by 20-120 min stimulation) enhances PMA/PHA-mediated phosphorylation of MEK1/2, ERK1/2, RSK, and JNK1/2, and modestly enhances Akt phosphorylation, in Jurkat T cells^[1].
BC12 (1-10 μM; 24 h) reduces viability of PMA/PHA-stimulated Jurkat T cells in a concentration-dependent manner, with 10 μM reducing viability to 65% after 24 h, though this reduction does not explain the near-complete inhibition of IL-2 secretion^[1].