133052-90-1

Basic information

• Product Name: GF109203X
• Synonyms: GO 6850;GO 6850 HCL;GF 109203X;GF-109203X HCL;GF109203X HYDROCHLORIDE;BISINDOLYLMALEIMIDE;BISINDOLYLMALEIMIDE I;BISINDOLYLMALEIMIDE I HYDROCHLORIDE
• CAS NO: 133052-90-1
• Molecular Formula: C25H24N4O2
• Molecular Weight: 412.48
• Product Categories: Protein Kinase;inhibitor;TGF-beta/Smad;Inhibitors;Smad;TGF-beta
• Mol File: 133052-90-1.mol

Chemical Properties

• Melting Point: 280℃ (decomposition)
• Boiling Point: 685.6 °C at 760 mmHg
• Flash Point: 368.5 °C
• Appearance: /
• Density: 1.3 g/cm³
• Vapor Pressure: 1.19E-18mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~1 mg/mlsoluble
• PKA: 8.13±0.60(Predicted)
• Water Solubility: Insoluble in water.
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 6 months.
• CAS DataBase Reference: GF109203X(CAS DataBase Reference)
• NIST Chemistry Reference: GF109203X(133052-90-1)
• EPA Substance Registry System: GF109203X(133052-90-1)

Safety Data

• Hazard Codes: Xn
• Statements: 40-22
• Safety Statements: 36/37
• WGK Germany: 3
• RTECS: UX9590000
• Hazardous Substances Data: 133052-90-1(Hazardous Substances Data)

Usage

Uses

Bisindolylmaleimide is used as a highly selective inhibitor of all PKC isoforms and slight inhibitor of GSK-3, used to selectively probe for PKC-mediated pathways for transduction of hormone, cytokine, and growth factor signals, very potent and selective inhibitor of protein kinase C.

Biological Activity

Very potent and selective inhibitor of protein kinase C, selective for the α and β 1 isoforms (IC 50 values are 0.0084, 0.0180, 0.210, 0.132, and 5.8 μ M for α , β 1, δ , ε , and ζ isoforms respectively). Selective over MLCK, PKG and PKA (IC 50 values are 0.6, 4.6, and 33 μ M respectively). Potent antagonist at the 5-HT 3 receptor (K i = 29.5 nM). Anti-inflammatory in vivo . Also available as part of the Mixed Kinase Inhibitor Tocriset? .

Biochem/physiol Actions

A potent and selective competitive inhibitor of protein kinase C (PKC) and of glycogen synthase kinase-3 (GSK-3). Inhibits parathyroid hormone-induced Ca2+ resorption from isolated bone tissue, Staurosporine, another protein kinase inhibitor, actually enhanced Ca2+ resorption elicited by a number of agents, but GF109203X counteracted that enhancement.

References

1) Toullec, et al. (1991), The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C; J. Biol .Chem. 266 15771 2) Hers, et al. (1999) The protein kinase C inhibitors bisindolylmaleimide I (GF 109203x) and IX (Ro 31-8220) are potent inhibitors of glycogen synthase kinase-3 activity; FEBS Lett. 460 433

InChI:InChI=1/C25H24N4O2.ClH/c1-28(2)12-7-13-29-15-19(17-9-4-6-11-21(17)29)23-22(24(30)27-25(23)31)18-14-26-20-10-5-3-8-16(18)20;/h3-6,8-11,14-15,26H,7,12-13H2,1-2H3,(H,27,30,31);1H

Upstream product

• 18372-22-0 2-(3-indolyl)oxoacetic acid methyl ester 
• 203719-69-1 1-(3-dimethylaminopropyl)indole-3-acetamide 
• 776262-13-6 2-(1H-indol-3-yl)-3-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-maleic acid anhydride 
• 133053-48-2 2-(1-tert.-butoxycarbonyl-1H-indol-3-yl)-3-[1-(3-dimethylaminopropyl)-1H-indol-3-yl)-N-methylmaleinimide 
• 119139-20-7 3-(1H-indol-3-yl)-4-[1-{tert-butyloxycarbonyl}indol-3-yl]-1-methyl-1H-pyrrole-2,5-dione 
• 109-54-6 3-(Dimethylamino)propyl chloride 
• 91026-01-6 2,3-bis(1H-indol-3-yl)-N-benzylmaleimide 
• 203719-61-3 3-[1-(3-O'-triphenylmethylpropyl)-3-indolyl]-4-(3-indolyl)-1H-pyrrole-2,5-dione 
• 22980-09-2 indolyl-3-glyoxylyl chloride 
• 1477-49-2 3-indolylglyoxylic acid 
• 120-72-9 indole 
• 170364-27-9 3-[1-(3-hydroxypropyl)-3-indolyl]-4-(3-indolyl)-1H-pyrrole-2,5-dione 
• 203719-67-9 1-(3-hydroxypropyl)indole-3-acetamide 
• 124-40-3 dimethyl amine 

Relevant articles and documents

Studies on cyclin-dependent kinase inhibitors: Indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides

A series of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1-CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3-a]pyrrolo[3,4-c]carbazoles are consistently more active (8-42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.

Synthesis of bisindolylmaleimides

The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors.

Synthesis of bisindolymaleimides

The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors. The reaction is very efficient and robust macrocyclization methodology.

Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure

New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein kinases were investigated, and the compound (21) with Ac- Cys-Pro-Lys-Lys-NHMe connected with the triethylene glycol spacer exhibited the most potent inhibition with relatively high selectivity.

Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them

The present invention provides bis-(1H-indol-3-yl)maleinimide derivatives and the pharmacologically acceptable salts thereof, processes for the preparation of these compounds, and pharmaceutical compositions containing them for the treatment of heart and blood vessel diseases, such as thromboses, arteriosclerosis, hypertension, of inflammatory processes, allergies, cancer, and certain degenerative damages of the central nervous system, as well as of diseases of the immune system and viral diseases.