Bisindolylmaleimide XI hydrochloride

Names

[ Name ]:
Bisindolylmaleimide XI hydrochloride

[Synonym ]:
3-{8-[(Dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl}-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione hydrochloride
3-{8-[(Dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl}-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione hydrochloride (1:1)
1H-Pyrrole-2,5-dione, 3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-4-(1-methyl-1H-indol-3-yl)-, hydrochloride (1:1)

Biological Activity

[Description]:

Bisindolylmaleimide XI hydrochloride (Ro 32-0432) is a potent, selective and orally active PKC inhibitor with IC50s of 9 nM, 28 nM, 31 nM, 37 nM, and 108 nM for PKCα, PKCβI, PKCβII, PKCγ, and PKCε, respectively[1][2].

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PKC

Research Areas >> Inflammation/Immunology

Signaling Pathways >> TGF-beta/Smad >> PKC

[Target]

PKC-α:9 nM (IC50)

PKC-βI:28 nM (IC50)

PKC-βII:31 nM (IC50)

PKC-γ:37 nM (IC50)

PKC-ε:108 nM (IC50)

[In Vitro]

Bisindolylmaleimide XI hydrochloride (Ro 32-0432) inhibits IL-2 secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells is also inhibited by Bisindolylmaleimide XI hydrochloride[2]. PKC inhibition with Bisindolylmaleimide XI hydrochloride (Ro 32-0432; 1 μM) decreases the proportion of apoptotic cells (-21%) in retinal progenitor cells (RPCs)[3].

[In Vivo]

Oral administration of Bisindolylmaleimide XI hydrochloride inhibits subsequent phorbol ester-induced edema in ratss. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis are also inhibited by Bisindolylmaleimide XI hydrochloride[2].

[References]

[1]. S E Wilkinson, et al. Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J. 1993 Sep 1;294 ( Pt 2)(Pt 2):335-7.

[2]. A M Birchall, et al. Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. J Pharmacol Exp Ther. 1994 Feb;268(2):922-9.

[3]. Roman Kholodenko, et al. Anti-apoptotic effect of retinoic acid on retinal progenitor cells mediated by a protein kinase A-dependent mechanism. Cell Res. 2007 Feb;17(2):151-62.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₈H₂₉ClN₄O₂

[ Molecular Weight ]:
489.01

[ Exact Mass ]:
488.197906

[ PSA ]:
59.27000

[ LogP ]:
4.95500

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

Inhibition of PTH desensitization by inhibition of the G protein-coupled receptor kinase-5 enzyme with Ro 32-0432. Moore, J.B., et al.

FASEB J. 12 , A741, (1998)

Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C.

Biochem. J. 294 , 335-337, (1993)

The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated a...

Cardiorespiratory responses to systemic administration of a protein kinase C inhibitor in conscious rats.

J. Appl. Physiol. 84 , 641-648, (1998)

Although protein kinase C (PKC) is an essential component of multiple neurally mediated events, its role in respiratory control remains undefined. The ventilatory effects of a systemically active PKC ...