Bisindolylmaleimide I (GF109203X), a potent and highly selective PCK inhibitor.

bisindolylmaleimide I is a potent and highly selective PCK inhibitor. bisindolylmaleimide I(GF-109203X )inhibits PKC isozymes alpha, beta 1, beta 2, gamma, delta and epsilon in vitro . GF-109203X inhibited GSK-3 in vitro, when assayed either in cell lysates (IC(50) 360 nM or in GSK-3beta immunoprecipitates (IC(50) 170 nM derived from rat epididymal adipocytes. Pretreatment of adipocytes with GF-109203X (5 microM) reduced GSK-3 activity in total cell lysates, to 25.1+/-4.3% of control.

Product information

CAS Number: 133052-90-1

Molecular Weight: 412.48

Formula: C25H24N4O2

Synonym:

GF109203X

GF-109203X

GF 109203X

Bisindolylmaleimide

GO 6850

GO-6850

GO6850

BIMI

Chemical Name: 3-(1-(3-(dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Smiles: CN(C)CCCN1C=C(C2=C(C3=CNC4=CC=CC=C34)C(=O)NC2=O)C2=CC=CC=C12

InChiKey: QMGUOJYZJKLOLH-UHFFFAOYSA-N

InChi: InChI=1S/C25H24N4O2/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)

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: ≥360 days 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:

Bisindolylmaleimide I is a competitive inhibitor with respect to ATP (Ki=14 nM) and displays high selectivity for PKC as compared to five different protein kinases. GF 109203X efficiently prevents PKC-mediated phosphorylations of an Mr=47, 000 protein in platelets and of an Mr=80, 000 protein in Swiss 3T3 cells. GF 109203X inhibits collagen- and a-thrombin-induced platelet aggregation as well as collagen-triggered ATP secretion. However, ADP-dependent reversible aggregation is not modified. In Swiss 3T3 fibroblasts, GF 109203X reverses the inhibition of epidermal growth factor binding induced by phorbol 12, 13-dibutyrate and prevents [3H] thymidine incorporation into DNA, only when this is elicited by growth promoting agents which activate PKC.

In Vivo:

Pial arteriole diameter changes are monitored using a closed cranial window in vivo microscopy technique. The pial arteriole dilatory response associated with SNS is decreased by 45%, when comparing DM vs either ND or TR rats. Also, pial arteriolar dilations to topical KCl and NS1619 are largely attenuated in DM rats, but not in ND or TR animals. These responses are completely restored by the acute application of Bisindolylmaleimide I to the brain surface. The PKC inhibitor has no effect on vascular responses in normoglycemic and TR animals. In conclusion, DM-associated chronic impairment of neurovascular coupling may be readily reversed by a PKC-α/β/γ inhibitor or prevented via pancreatic islet transplantation. Specific PCK isoforms (α/β/γ) are believed to be mechanistically linked to the neurovascular uncoupling seen with hyperglycemia.

References:

1. Harmati G, Papp F, Szentandrássy N, Bárándi L, Ruzsnavszky F, Horváth B, Bányász T, Magyar J, Panyi G, Krasznai Z, Nánási PP. Effects of the PKC inhibitors chelerythrine and bisindolylmaleimide I (GF 109203X) on delayed rectifier K+ currents. Naunyn Schmiedebergs Arch Pharmacol. 2011 Feb;383(2):141-8. doi: 10.1007/s00210-010-0584-8. Epub 2010 Dec 1. PubMed PMID: 21120453.
2. Hers I, Tavaré JM, Denton RM. 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. 1999 Nov 5;460(3):433-6. PubMed PMID: 10556511.
3. Stemmelin J, Mathis C, Ungerer A. GF 109203X, a selective inhibitor of protein kinase C, impairs retention performance in an operant task. Neuroreport. 1999 Sep 9;10(13):2805-9. PubMed PMID: 10511444.
4. Alessi DR. The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent inhibitors of MAPKAP kinase-1beta (Rsk-2) and p70 S6 kinase. FEBS Lett. 1997 Feb 3;402(2-3):121-3. PubMed PMID: 9037179.
5. Gekeler V, Boer R, Uberall F, Ise W, Schubert C, Utz I, Hofmann J, Sanders KH, Schächtele C, Klemm K, Grunicke H. Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance. Br J Cancer. 1996 Sep;74(6):897-905. PubMed PMID: 8826855; PubMed Central PMCID: PMC2074754.

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