133052-90-1 Usage
Description
GF-109203X (133052-90-1) is a potent and selective protein kinase C inhibitor (IC50 = 10 nM; cAMP-dependent protein kinase IC50 = 2 μM and phosphorylase kinase IC50 = 0.7 μM). Inactive against the tyrosine kinases EGFR, PGDFR and Insulin receptor. Potent inhibitor of GSK-3β in cell lysates (IC50 = 360nM) and GSK-3β immunoprecipitates (IC50 = 170nM) derived from rat epididymal adipocytes.2 Cell permeable.
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
Check Digit Verification of cas no
The CAS Registry Mumber 133052-90-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,3,0,5 and 2 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 133052-90:
(8*1)+(7*3)+(6*3)+(5*0)+(4*5)+(3*2)+(2*9)+(1*0)=91
91 % 10 = 1
So 133052-90-1 is a valid CAS Registry Number.
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
133052-90-1Relevant articles and documents
Studies on cyclin-dependent kinase inhibitors: Indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides
Sanchez-Martinez, Concha,Shih, Chuan,Zhu, Guoxin,Li, Tiechao,Brooks, Harold B.,Patel, Bharvin K. R.,Schultz, Richard M.,DeHahn, Tammy B.,Spencer, Charles D.,Watkins, Scott A.,Ogg, Catherine A.,Considine, Eileen,Dempsey, Jack A.,Zhang, Faming
, p. 3841 - 3846 (2007/10/03)
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.
A New, Efficient Method for the Synthesis of Bisindolylmaleimides
Faul, Margaret M.,Winneroski, Leonard L.,Krumrich, Christine A.
, p. 6053 - 6058 (2007/10/03)
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Synthesis of bisindolymaleimides
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, (2008/06/13)
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.
