For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>Bisindolylmaleimide I (GF109203X) is a highly selective, cell-permeable, and reversible protein kinase C (PKC) inhibitor with a Ki value of 14 nM.<br>IC50 & Target: 20±7 nM (PKC α), 17±5 nM (PKC βⅠ), 16±5 nM (PKC βⅡ), 20±5 nM (PKC γ)[1].<br>Ki & Target: 14 nM (PKC)[1].<br>InVitro: GF109203X 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[1].<br>InVivo: 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 GF109203X 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[2].</p>
| Catalog Number | I001259 |
| CAS Number | 133052-90-1 |
| Synonyms | 3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione |
| Molecular Formula | C₂₅H₂₄N₄O₂ |
| Purity | ≥95% |
| Target | TGF-beta/Smad |
| Solubility | DMSO |
| Storage | Store at RT |
| InChI | CN(C)CCCN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CNC5=CC=CC=C54 |
| InChIKey | QMGUOJYZJKLOLH-UHFFFAOYSA-N |
| SMILES | 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) |
| Reference | </br>1:Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy. Kosgodage US, Trindade RP, Thompson PR, Inal JM, Lange S.Int J Mol Sci. 2017 May 9;18(5). pii: E1007. doi: 10.3390/ijms18051007. PMID: 28486412 Free Article</br>2:Effects of the PKC inhibitors chelerythrine and bisindolylmaleimide I (GF 109203X) on delayed rectifier K+ currents. Harmati G, Papp F, Szentandrássy N, Bárándi L, Ruzsnavszky F, Horváth B, Bányász T, Magyar J, Panyi G, Krasznai Z, Nánási PP.Naunyn Schmiedebergs Arch Pharmacol. 2011 Feb;383(2):141-8. doi: 10.1007/s00210-010-0584-8. Epub 2010 Dec 1. PMID: 21120453 </br>3:Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins. Krejci P, Masri B, Salazar L, Farrington-Rock C, Prats H, Thompson LM, Wilcox WR.J Biol Chem. 2007 Feb 2;282(5):2929-36. Epub 2006 Dec 4. PMID: 17145761 Free Article</br>4:The protein kinase C inhibitor, bisindolylmaleimide (I), inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells. Park WS, Son YK, Ko EA, Ko JH, Lee HA, Park KS, Earm YE.Life Sci. 2005 Jun 17;77(5):512-27. Epub 2005 Feb 25. PMID: 15904669 </br>5:Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X). Thomas D, Hammerling BC, Wimmer AB, Wu K, Ficker E, Kuryshev YA, Scherer D, Kiehn J, Katus HA, Schoels W, Karle CA.Cardiovasc Res. 2004 Dec 1;64(3):467-76. PMID: 15537500 </br>6:Chelerythrine and bisindolylmaleimide I prolong cardiac action potentials by protein kinase C-independent mechanism. Voutilainen-Myllylä S, Tavi P, Weckström M.Eur J Pharmacol. 2003 Apr 11;466(1-2):41-51. PMID: 12679140 </br>7:Bisindolylmaleimide I and V inhibit necrosis induced by oxidative stress in a variety of cells including neurons. Asakai R, Aoyama Y, Fujimoto T.Neurosci Res. 2002 Nov;44(3):297-304. PMID: 12413658 </br>8:Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors. Chou AH, Howard BD.Oncogene. 2002 Sep 12;21(41):6348-55. PMID: 12214275 Free Article</br>9:Inhibition of acetylcholine-activated K(+) current by chelerythrine and bisindolylmaleimide I in atrial myocytes from mice. Cho H, Youm JB, Earm YE, Ho WK.Eur J Pharmacol. 2001 Jul 27;424(3):173-8. PMID: 11672559 </br>10:Divergent effects of protein kinase C (PKC) inhibitors staurosporine and bisindolylmaleimide I (GF109203X) on bone resorption. Lee SK, Stern PH.Biochem Pharmacol. 2000 Oct 1;60(7):923-6. PMID: 10974200 |
