138489-18-6

138489-18-6 structure

Name: Ro-318220
Chemical Name: Bisindolylmaleimide IX mesylate
CAS Number: 138489-18-6
Molecular Formula: C₂₆H₂₇N₅O₅S₂
Molecular Weight: 553.65
Catalog: Biochemical Inhibitor TGF-beta/Smad signaling pathway inhibitor (TGF-beta/Smad) PKC inhibitor
Create Date: 2017-01-28 16:34:14
Modify Date: 2024-01-03 13:37:41
Ro 31-8220 mesylate is a potent PKC inhibitor, with IC50s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β

Name	Bisindolylmaleimide IX mesylate
Synonyms	Ro 31-8220 3-Methyl-3-tert-pentylamino-1-butyne 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 Bisindolylmaleimide IX Mesylate 3-{3-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate 3-t-Amylamino-3-methylbutin 3-tert-Amylamino-3-methyl-but-1-in Ro-318220 N-tert-Amyl-1,1-dimethylpropargylamine 3-<1.1-Dimethyl-propylamino>-3-methyl-1-butin Tert.-amyl-3.3-dimethylpropyne-1-ylamin 3-tert.-Amylamino-3-methyl-1-butin Ro 31-8220 mesylate Ro 31-8220 (mesylate)

Description	Ro 31-8220 mesylate is a potent PKC inhibitor, with IC50s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β
Related Catalog	Signaling Pathways >> Epigenetics >> PKC Signaling Pathways >> TGF-beta/Smad >> PKC Research Areas >> Cardiovascular Disease Research Areas >> Neurological Disease
Target	PKC-α:5 nM (IC50) PKC-βI:24 nM (IC50) PKC-βII:14 nM (IC50) PKC-γ:27 nM (IC50) PKC-ε:24 nM (IC50) Rat Brain PKC:23 nM (IC50) MAPKAP-K1b:3 nM (IC50) MSK1:8 nM (IC50) S6K1:15 nM (IC50) GSK3β:38 nM (IC50)
In Vitro	Ro 31-8220 mesylate is a potent PKC inhibitor, with IC50s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively[1]. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β (IC50s, 3, 8, 15, and 38 nM, respectively), with no effect on MKK3, MKK4, MKK6 and MKK7. Moreover, Ro 31-8220 directly suppresses voltage-dependent Na+ channels[2]. Ro 31-8220 (1 μM) is neuroprotective against paraoxon-induced neuronal cell death in cerebellar granule neurons, blocks paraoxon-induced caspase-3 activity, and reduces the paraoxon-induced increase in phospho-PKC pan levels[3].
In Vivo	Ro 31-8220 (6 mg/kg/d, s.c.) is well tolerated, and has half-life of 5.7 hours in mice. Ro 31-8220-treated MLP−/− mice show a dramatic rescue in fractional shortening after treatment for 6 weeks, but the WT mice shows no change[4].
Cell Assay	A neurotoxic concentration of paraoxon (200 μM) is added to the granule cell cultures for the indicated time on day in vitro (DIV) 8. The following drugs are added to the granule cell cultures prior to or after paraoxon exposure on DIV 8: Ro-81-3220 (1 μM) is added 15 min prior to or 3 h after the addition of paraoxon. TPA (0.1 μM) is added 15 min prior to the addition of paraoxon[1].
Animal Admin	Mice[4] The affects of long-term Ro 31-8220 administration over 4 to 6 weeks in MLP−/− heart failure mice are investigated. All mice are assessed for ventricular performance by echocardiography at the beginning of the study and 6 weeks later. Ro 31-8220 (or vehicle) is injected subcutaneously once per day at a dosage of 6 mg/kg/d[4].
References	[1]. Wilkinson SE, et al. Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J. 1993 Sep 1;294 (Pt 2):335-7. [2]. Davies SP, et al. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105. [3]. Tian F, et al. Inhibition of protein kinase C protects against paraoxon-mediated neuronal cell death. Neurotoxicology. 2007 Jul;28(4):843-9. Epub 2007 Apr 20. [4]. Hambleton M, et al. Pharmacological- and gene therapy-based inhibition of protein kinase Calpha/beta enhances cardiac contractility and attenuates heart failure. Circulation. 2006 Aug 8;114(6):574-82.

Density	1.4±0.1 g/cm3
Molecular Formula	C₂₆H₂₇N₅O₅S₂
Molecular Weight	553.65
PSA	131.20000
LogP	3.95
Index of Refraction	1.740
Storage condition	0-6°C