Ro-31-8220

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H23N5O2S
Molecular Weight	457.547
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C(C2=C1C=CC=C2)C3=C(C(=O)NC3=O)C4=CN(CCCSC(N)=N)C5=CC=CC=C45

InChI

InChIKey=DSXXEELGXBCYNQ-UHFFFAOYSA-N

InChI=1S/C25H23N5O2S/c1-29-13-17(15-7-2-4-9-19(15)29)21-22(24(32)28-23(21)31)18-14-30(11-6-12-33-25(26)27)20-10-5-3-8-16(18)20/h2-5,7-10,13-14H,6,11-12H2,1H3,(H3,26,27)(H,28,31,32)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12805057
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21943284 | https://www.ncbi.nlm.nih.gov/pubmed/10998351 | https://www.ncbi.nlm.nih.gov/pubmed/16302800 |

RO-31-8220 is a cell-permeable staurosporine analog, that shows potent inhibition of PKC α, PKC βI, PKC βII, PKC γ, and PKC ε. Ro 31-8220 also inhibits MSK1, MAPKAPK1, RSK, GSK3β, and S6K1 with a potency similar to that for PKC. Ro 31-8220 alters cellular protein kinase C localization and potently inhibits the growth of A549 and MCF-7 cells with IC50 of 0.78 μM and 0.897 μM, respectively. RO 31-8220 enhances epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. Ro 31-8220 significantly decreases apoE secretion from primary human macrophages by inhibiting vesicular transport of apoE to the plasma membrane without significantly affecting apoE mRNA or apoE protein levels.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Glycogen synthase kinase-3 beta 51 Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18929433	Inhibitor 8297	2.8 nM [IC50]
Serine/threonine-protein kinase PIM1 13 Target ID: CHEMBL2147 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302800	Inhibitor 8297	8.0 nM [Kd]
Ribosomal protein S6 kinase alpha 3 5 Target ID: CHEMBL2345 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21488662	Inhibitor 8297	10.0 nM [IC50]
Ribosomal protein S6 kinase 1 4 Target ID: CHEMBL4501 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10998351	Inhibitor 8297	15.0 nM [IC50]
Ribosomal protein S6 kinase alpha 5 4 Target ID: CHEMBL4237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10998351	Inhibitor 8297	8.0 nM [IC50]
Protein kinase C alpha 20 Target ID: CHEMBL299 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10998351	Inhibitor 8297	15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Studies on the mechanism of fibrate-inhibited expression of plasminogen activator inhibitor-1 in cultured hepatocytes from cynomolgus monkey.	1997 Jan	9012633
Protein phosphatase-protein kinase interplay modulates alpha 1b-adrenoceptor phosphorylation: effects of okadaic acid.	2000 Feb	10683197
ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells.	2000 Mar	10712238
Regulation of SP-B and SP-C secretion in rat type II cells in primary culture.	2001 Dec	11704537
Cadmium-induced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun, and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species.	2001 Jun	11353138
Phosphorylation is involved in the activation of metal-regulatory transcription factor 1 in response to metal ions.	2001 Nov 9	11551972
Gene expression profile in BALB/c-3T3 cells transformed with beryllium sulfate.	2001 Sep	11568973
Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells.	2003 Mar 15	12605413
Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity.	2003 Oct	14511371
Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin.	2004 Feb 1	15037193
Roles of protein kinase C, Ca2+, Pyk2, and c-Src in agonist activation of rat lacrimal gland p42/p44 MAPK.	2006 Aug	16877402
P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1.	2006 Aug	16236484
Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells.	2006 Feb	16280361
Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species.	2006 Jul 1	16757516
Zinc is required for Fc epsilon RI-mediated mast cell activation.	2006 Jul 15	16818790
Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells.	2006 Sep 15	17000667
Evidence that tumor necrosis factor-related apoptosis-inducing ligand induction by 5-Aza-2'-deoxycytidine sensitizes human breast cancer cells to adriamycin.	2007 Feb 1	17283156
A genomic screen for activators of the antioxidant response element.	2007 Mar 20	17360324
Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells.	2008 Apr	18048804
PKC promotes proliferation of airway smooth muscle cells by regulating cyclinD1 expression in asthmatic rats.	2008 Jun	18501114
Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.	2008 Jun	18357586
Differential effects of tumor necrosis factor-alpha and interleukin-1beta on cell death in human articular chondrocytes.	2008 Jun	18054255
Progress in allergy signal research on mast cells: up-regulation of histamine signal-related gene expression in allergy model rats.	2008 Mar	18360087
Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells.	2008 Mar	18058799
Differential roles of MAPKs and MSK1 signalling pathways in the regulation of c-Jun during phenylephrine-induced cardiac myocyte hypertrophy.	2009 Feb	19002563
A role for Rho-kinase in Ca-independent contractions induced by phorbol-12,13-dibutyrate.	2009 Mar	18986333
Mechanism of action of the stimulatory effect of apigenin-6-C-(2''-O-alpha-l-rhamnopyranosyl)-beta-L-fucopyranoside on 14C-glucose uptake.	2009 May 15	19070612
Nitro-aspirin inhibits MCF-7 breast cancer cell growth: effects on COX-2 expression and Wnt/beta-catenin/TCF-4 signaling.	2009 Nov 15	19576865
All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-delta.	2011 Aug	21393419
Molecular investigation of the effects of lindane in rat hepatocytes: microarray and mechanistic studies.	2011 Dec	22001173
SHAFTS: a hybrid approach for 3D molecular similarity calculation. 2. Prospective case study in the discovery of diverse p90 ribosomal S6 protein kinase 2 inhibitors to suppress cell migration.	2011 May 26	21488662
MAPK- and PKC/CREB-dependent induction of interleukin-11 by the environmental contaminant formaldehyde in human bronchial epithelial cells.	2012 Feb 6	22138297
Novel Nrf2/ARE activator, trans-Coniferylaldehyde, induces a HO-1-mediated defense mechanism through a dual p38α/MAPKAPK-2 and PK-N3 signaling pathway.	2015 Sep 21	26275128

Patents

Sample Use Guides

In Vivo Use Guide

MLP−/− Mice were treated with Ro 31-8220 at dose 6 mg/kg/d, s.c.

Route of Administration: Other

In Vitro Use Guide

To compare the effect of PKC inhibition or downregulation on neuritogenesis, at 24 h after plating, the neuroblastoma x •glioma NG108-15 hybrid cells were placed in serum free high-glucose DMEM supplemented with 0.015% dimethyl sulfoxide (DMSO) (control) or 1 mkm Go6983 plus 1 mkm Ro318220 to inhibit PKCs or with 300 nm PMA to downregulate PKCs, and morphological changes were examined after 24 or 48 h.

Name

Type

Language

Ro-31-8220

Code

English

CARBAMIMIDOTHIOIC ACID, 3-(3-(2,5-DIHYDRO-4-(1-METHYL-1H-INDOL-3-YL)-2,5-DIOXO-1H-PYRROL-3-YL)-1H-INDOL-1-YL)PROPYL ESTER

Systematic Name

English

BISINDOLYLMALEIMIDE IX

Common Name

English

RO 31-8220

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2089