BISINDOLYLMALEIMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H13N3O2
Molecular Weight	327.3361
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1NC(=O)C(C2=CNC3=C2C=CC=C3)=C1C4=CNC5=C4C=CC=C5

InChI

InChIKey=DQYBRTASHMYDJG-UHFFFAOYSA-N

InChI=1S/C20H13N3O2/c24-19-17(13-9-21-15-7-3-1-5-11(13)15)18(20(25)23-19)14-10-22-16-8-4-2-6-12(14)16/h1-10,21-22H,(H,23,24,25)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1732526 | https://www.ncbi.nlm.nih.gov/pubmed/7592032 | https://www.ncbi.nlm.nih.gov/pubmed/8081852 | https://www.ncbi.nlm.nih.gov/pubmed/9851596 | https://www.ncbi.nlm.nih.gov/pubmed/22043317

Bisindolylmaleimide IV is a cell-permeable potent and somewhat selective inhibitor of PKC (IC50 = 87 nM), designed to be more selective than the general protein kinase inhibitor staurosporine (sc-3510). However, bisindolymaleimide IV also inhibits protein kinase A (PKA), with an IC50 = 2.7 uM. Bisindolylmaleimide IV was very weak and inhibited [3H] N-methyl scopolamine binding only at the highest concentration used. Bbisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Protein kinase C (PKC) 44 Target ID: CHEMBL2093867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1732526 \| https://www.ncbi.nlm.nih.gov/pubmed/22043317	Inhibitor 8504	190.0 nM [IC50]
Protein kinase C beta 22 Target ID: CHEMBL3045 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15380221	Inhibitor 8504	212.0 nM [IC50]
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27845365	Inhibitor 8504	25.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms.	2001-08-03	11397799
The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A.	2001-07-01	11377403
Role of zinc in pulmonary endothelial cell response to oxidative stress.	2001-07	11404267
Post-ischemic PKC inhibition impairs myocardial calcium handling and increases contractile protein calcium sensitivity.	2001-07	11399253
Calyculin-A induces focal adhesion assembly and tyrosine phosphorylation of p125(Fak), p130(Cas), and paxillin in Swiss 3T3 cells.	2001-07	11382927
DNA binding of TEA/ATTS domain factors is regulated by protein kinase C phosphorylation in human choriocarcinoma cells.	2001-06-29	11313339
Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments.	2001-06-22	11292825
Protein kinase C-mediated down-regulation of MDR3 mRNA expression in Chang liver cells.	2001-06-01	11331069
TSH-induced differentiated functions correlate with enhancement of phosphotyrosine phosphatase activity in thyroid cells. Effect of phorbol 12-myristate 13-acetate.	2001-06	11375131
Possible involvement of Rho kinase in Ca2+ sensitization and mobilization by MCh in tracheal smooth muscle.	2001-06	11350801
Calcium-sensing receptor activation induces intracellular calcium oscillations.	2001-06	11350736
Hypoxia alters the sensitivity of the L-type Ca(2+) channel to alpha-adrenergic receptor stimulation in the presence of beta-adrenergic receptor stimulation.	2001-05-25	11375273
Receptor-mediated inhibition of G protein-coupled inwardly rectifying potassium channels involves G(alpha)q family subunits, phospholipase C, and a readily diffusible messenger.	2001-05-18	11279027
Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways.	2001-05-11	11348997
Phosphorylation of murine homeodomain protein Dlx3 by protein kinase C.	2001-05-04	11343707
Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells.	2001-05	11380080
Analysis of the signal pathways involved in the regulation of fatty acid synthase gene expression by insulin and somatotropin.	2001-05	11374539
Effects of insulin-like growth factor-1 on retinal endothelial cell glucose transport and proliferation.	2001-05	11359881
Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures.	2001-05	11359865
Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver.	2001-05	11343250
Protein kinase C regulation of dopamine transporter initiated by nicotinic receptor activation in slices of rat prefrontal cortex.	2001-05	11331413
Leukotriene D(4) affects localisation of vinculin in intestinal epithelial cells via distinct tyrosine kinase and protein kinase C controlled events.	2001-05	11329379
Induction of embryonic dysmorphogenesis by high glucose concentration, disturbed inositol metabolism, and inhibited protein kinase C activity.	2001-05	11320530
Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle.	2001-05	11299216
Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier against oxidants.	2001-05	11292590
Differential effects of growth hormone and insulin-like growth factor I on human endothelial cell migration.	2001-05	11287339
Pertussis toxin directly activates endothelial cell p42/p44 MAP kinases via a novel signaling pathway.	2001-05	11287337
Protein kinase C-mediated desensitization of the neurokinin 1 receptor.	2001-05	11287322
Hypoxic enhancement of evoked noradrenaline release from the human neuroblastoma SH-SY5Y.	2001-04-18	11311975
Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus.	2001-04-15	11290600
Altered expression of glutamate transporters under hypoxic conditions in vitro.	2001-04-15	11288147
Use of A-192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy.	2001-04-13	11334846
Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.	2001-04-13	11304492
Modulation of rat erg1, erg2, erg3 and HERG K+ currents by thyrotropin-releasing hormone in anterior pituitary cells via the native signal cascade.	2001-04-01	11283231
Chemorepellent signaling through the PACAP/lysozyme receptor is mediated through cAMP and PKC in Tetrahymena thermophila.	2001-04	11401196
Protein kinase C alpha modulates the Ca2+ influx phase of the Ca2+ response to 1alpha,25-dihydroxy-vitamin-D3 in skeletal muscle cells.	2001-04	11383922
Phorbol ester differentially regulates oxytocin receptor binding activity in hypothalamic cultured neurons and astrocytes.	2001-04	11311739
Signal transduction pathways for activation of extracellular signal-regulated kinase by arachidonic acid in rat neutrophils.	2001-04	11310854
Mechanisms of thrombin-induced MAPK activation associated with cell proliferation in human cultured tracheal smooth muscle cells.	2001-04	11306243
Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels.	2001-04	11300649
The role of protein kinase C in the regulation of serotonin-2A receptor expression.	2001-04	11299321
Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C.	2001-04	11298324
Cyclization strategies for the synthesis of macrocyclic bisindolylmaleimides.	2001-03-23	11300896
Thrombin activates p38 mitogen-activated protein kinase in vascular smooth muscle cells.	2001-03-16	11388701
Upregulation of p21(WAF1/CIP1) leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1.	2001-03-08	11313866
Progesterone effect mediated by the voltage-dependent calcium channel and protein kinase C on noncapacitated cryopreserved bovine spermatozoa.	2001-03	11350374
ATP stimulated cyclic AMP formation in bovine chromaffin cells is enhanced by neuropeptide Y.	2001-03	11287099
Protein kinase C-dependent and -independent inhibition of Ca(2+) influx by phorbol ester in rat pancreatic beta-cells.	2001-03	11282458
Potent direct inhibition of mammalian phospholipase D isoenzymes by calphostin-c.	2001-02-27	11327888
Protein tyrosine kinase-dependent regulation of adenylate cyclase and phosphatidylinositol 3-kinase activates the expression of glial fibrillary acidic protein upon induction of differentiation in rat c6 glioma.	2001	11401334

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Bisindolylmaleimide IV inhibits protein kinase C (PKC) with IC50 values from 0.10 to 0.55 uM.

Name

Type

Language

BISINDOLYLMALEIMIDE

Systematic Name

English

3,4-DI-1H-INDOL-3-YL-1H-PYRROLE-2,5-DIONE

Preferred Name

English

BISINDOLYLMALEIMIDE IV

Common Name

English

Code System Code Type Description

CAS

119139-23-0