557520

Ro-31-8220

A cell-permeable, reversible, competitive, and selective inhibitor of protein kinase C (PKC; IC₅₀ = 10 nM) over CaM kinase II (IC₅₀ = 17 µM) and protein kinase A (IC₅₀ = 900 nM).

• Synonym(s): Ro-31-8220, 3-[1-[3-(Amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide, Bisindolylmaleimide IX, Methanesulfonate
• Empirical Formula (Hill Notation): C₂₅H₂₃N₅O₂S · xCH₄O₃S
• CAS Number: 138489-18-6
• Molecular Weight: 457.55 (free base basis)
• MDL number: MFCD03788207
• UNSPSC Code: 12352202
• NACRES: NA.77
• Assay: ≥95% (HPLC)
• Form: solid
• Quality level: 100
• Storage condition: OK to freeze, desiccated (hygroscopic), protect from light

Properties

• Quality Level: 100
• assay: ≥95% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, desiccated (hygroscopic), protect from light
• color: red
• solubility: water: 1 mg/mL, DMSO: 100 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: [S](=O)(=O)(O)C.S(CCC[n]1c2c(c(c1)C3=C(C(=O)NC3=O)c4c5c([n](c4)C)cccc5)cccc2)\C(=N\[H])\N
• 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)
• InChI key: SAWVGDJBSPLRRB-UHFFFAOYSA-N

Description

General description

A cell-permeable, competitive, reversible, and selective inhibitor of protein kinase C (PKC; IC₅₀ = 10 nM) over CaM kinase II (IC₅₀ = 17 µM) and protein kinase A (IC₅₀ = 900 nM). Potently inhibits GSK-3 in primary adipocytes (IC₅₀ = 6.8 nM) and in GSK-3β immunoprecipitates (IC₅₀ 2.8 nM). An inhibitor of MAP kinase phosphatase-1 expression and an activator of JNK1. Inhibits the phosphorylation of Raf-1 and induces apoptosis, independent of its effects on PKC, in HL-60 cells. Also inhibits sirtuin in a NAD-competitive manner (IC₅₀ = 3.5 µM and 0.8 µM for SIRT1 and SIRT2, respectively), and induces hyperacetylation of tubulin in A549 cells.

A cell-permeable, reversible, competitive, and selective inhibitor of protein kinase C (PKC; IC₅₀ = 10 nM) over CaM kinase II (IC₅₀ = 17 µM) and protein kinase A (IC₅₀ = 900 nM). Potently inhibits GSK-3 in primary adipocytes (IC₅₀ = 6.8 nM) and in GSK-3β immunoprecipitates (IC₅₀ = 2.8 nM). An inhibitor of MAP kinase phosphatase-1 expression and an activator of JNK1. Inhibits the phosphorylation of Raf-1 and induces apoptosis, independent of its effects on PKC, in HL-60 cells. Also inhibits sirtuin in a NAD-competitive manner (IC₅₀ = 3.5 µM and 0.8 µM for SIRT1 and SIRT2, respectively), and induces hyperacetylation of tubulin in A549 cells. A 5 mM (500 µg/181 µl) solution of Ro-31-8220 (Cat. No. 557521) in H₂O is also available.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
PKC

Product competes with ATP.

Reversible: yes

Target IC₅₀: 10 nM, 17 µM, 900 nM against PKC, CaM kinase II, and protein kinase A, respectively; 6.8 nM against GSK-3 in primary adipocytes; 2.8 nM against GSK-3β immunoprecipitates)

Preparation Note

Following reconstitution, aliquot and freeze (-20°C). DMSO stock solutions are stable for up to 4 months at -20°C.

Other Notes

Trapp, J., et al. 2006. J. Med. Chem.In press.
Powell, D.J., et al. 2003. Mol. Cell Biol.23, 7794.
Han, Z., et al. 2000. Cell Death Differ.7, 521.
Hers, I., et al. 1999. FEBS Lett.460, 433.
Beltman, J., et al. 1996. J. Biol. Chem. 271, 27018.
Keller, H.U., and Niggli, V. 1993. Biochem. Biophys. Res. Commun.194, 1111.
McKenna, J.P., and Hanson, P.J. 1993. Biochem. Pharmacol.46, 583.
Davis, P.D., et al. 1992. J. Med. Chem. 35, 994.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 2
• flash_point_f: Not applicable
• flash_point_c: Not applicable