Ro 31-8220 mesylate

Ro 31-8220 is a PKC-inhibitor, which inhibits stimulated fluid pinocytosis of human PMNs induced by the PKC-activators phorbol myristate acetate (PMA, IC50 = 1.35 x 10(-6) M) or diacylglycerols (OAG, diC8) by 95%. Ro-31-8220 showed the apoptotic effect on HL-60 cells, which was mediated by a well-characterized transduction process of apoptotic signals: i.e., mitochondrial cytochrome c efflux and the activation of caspase-3 in the cytosol. Moreover, the ability of Ro-31-8220 to induce apoptotic activation was completely inhibited by the over-expression of the apoptotic suppressor gene, Bcl-2, in the cells.

Product information

CAS Number: 138489-18-6

Molecular Weight: 553.65

Formula: C26H27N5O5S2

Synonym:

RO31-8220

RO31-8220 mesylate

Bisindolylmaleimide IX

BIM IX.

Chemical 

Related CAS Number:

125314-64-9 (free base)

Chemical Name: 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 methanesulfonate

Smiles: CN1C=C(C2=C(C3=CN(CCCSC(N)=N)C4=CC=CC=C43)C(=O)NC2=O)C2=CC=CC=C12.CS(O)(=O)=O

InChiKey: SAWVGDJBSPLRRB-UHFFFAOYSA-N

InChi: InChI=1S/C25H23N5O2S.CH4O3S/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;1-5(2,3)4/h2-5,7-10,13-14H,6,11-12H2,1H3,(H3,26,27)(H,28,31,32);1H3,(H,2,3,4)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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. 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. 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.

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.

References:

1. Kim SY, Kim S, Kim JM, Jho EH, Park S, Oh D, Yun-Choi HS. PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. BMB Rep. 2011 Feb;44(2):140-5. doi: 10.5483/BMBRep.2011.44.2.140. PubMed PMID: 21345315.
2. Marmy-Conus N, Hannan KM, Pearson RB. Ro 31-6045, the inactive analogue of the protein kinase C inhibitor Ro 31-8220, blocks in vivo activation of p70(s6k)/p85(s6k): implications for the analysis of S6K signalling. FEBS Lett. 2002 May 22;519(1-3):135-40. PubMed PMID: 12023032.
3. Chepurny OG, Hussain MA, Holz GG. Exendin-4 as a stimulator of rat insulin I gene promoter activity via bZIP/CRE interactions sensitive to serine/threonine protein kinase inhibitor Ro 31-8220. Endocrinology. 2002 Jun;143(6):2303-13. PubMed PMID: 12021195; PubMed Central PMCID: PMC3500996.
4. Han Z, Pantazis P, Lange TS, Wyche JH, Hendrickson EA. The staurosporine analog, Ro-31-8220, induces apoptosis independently of its ability to inhibit protein kinase C. Cell Death Differ. 2000 Jun;7(6):521-30. PubMed PMID: 10822275.
5. Zhou B, Zhang JP, Hu ZL, Tan YX, Qian DH. Ro 31-8220 inhibits release of interleukin-1 and interleukin-6 from mouse peritoneal macrophages induced by fibrin fibrinogen degradation products. Zhongguo Yao Li Xue Bao. 1999 May;20(5):449-51. PubMed PMID: 10678095.
6. Lingameneni R, Vysotskaya TN, Duch DS, Hemmings HC Jr. Inhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor. FEBS Lett. 2000 May 12;473(2):265-8. PubMed PMID: 10812087.

Products are for research use only. Not for human use.