Ro-318220

Names

[ Name ]:
Ro-318220

[Synonym ]:
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)

Biological Activity

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ 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

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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