Bisindolylmaleimide I hydrochloride

Bisindolylmaleimide I (BIM I) is a highly selective, cell-permeable, and reversible PKC inhibitor (K_i = 14 nM) that is structurally similar to the poorly selective PKC inhibitor staurosporine . It acts as a competitive inhibitor for the ATP binding site of PKC and shows high selectivity for PKCα, β1, β2, γ, δ, and ε isozymes. BIM I directly inhibits glycogen synthase kinase 3 (GSK3) in primary adipocyte lysates (IC₅₀ = 360 nM) and in GSK3β immunoprecipitates derived from rat epididymal adipocytes (IC₅₀ = 170 nM). It also competitively antagonizes the serotonin (5-HT) receptor subtype 5-HT₃ with a K_i value of 61 nM.

GF 109203X hydrochloride has been used to inhibit protein kinase C in human neuroblastoma-derived kelly cells.

GF 109203X prevents collagen-triggered adenosine and three phosphate (ATP) secretion. It also inhibits collagen and α-thrombin-induced platelet aggregation. It functions as an inhibitor of glycogen synthase kinase-3 (GSK-3). GF 109203X also functions as an anti-inflammatory agent.

Inhibitor of protein kinase C; potent inhibitor of GSK-3.

Bovine brain PKC: 10 nM (IC₅₀); PKC-βII: 16 nM (IC₅₀); PKC-βI: 17 nM (IC₅₀); PKCα: 20 nM (IC₅₀); PKCγ: 20 nM (IC₅₀); FDGFG: 65 μM (IC₅₀)

[1] D. TOULLEC. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.[J]. The Journal of Biological Chemistry, 1991, 12 1: 15771-15781. DOI: 10.1016/s0021-9258(18)98476-0
[2] INGEBORG HERS  Richard M D  Jeremy M Tavaré. The protein kinase C inhibitors bisindolylmaleimide I (GF 109203x) and IX (Ro 31-8220) are potent inhibitors of glycogen synthase kinase-3 activity[J]. FEBS Letters, 1999, 460 3: 433-436. DOI: 10.1016/s0014-5793(99)01389-7
[3] S J COULTRAP. Competitive antagonism of the mouse 5-hydroxytryptamine3 receptor by bisindolylmaleimide I, a “selective” protein kinase C inhibitor.[J]. Journal of Pharmacology and Experimental Therapeutics, 1999, 290 1: 76-82.