Bisindolylmaleimide IV is a potent cell-permeable inhibitor of protein kinase C (PKC) with IC50 values are 0.1- 0.55μM[1]. Bisindolylmaleimide IV inhibits the cAMP-dependent protein kinase (PKA) with IC50 ranging from 3.1-11.8μM[2]. Bisindolylmaleimide IV is primarily used in research related to cancer biology[3], cardiovascular diseases[4], and diabetes, particularly in studies investigating PKC-mediated signaling pathways and their impact on cellular functions[5].
Bisindolylmaleimide IV (20μM) down-regulates cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIPL) expression and facilitates CD95-mediated apoptosis in monocyte-derived dendritic cells[6]. Bisindolylmaleimide IV (0.1-100μM) inhibits the release of reactive oxygen species (ROS) from human neutrophils stimulated by agents such as IL-3, phorbol-12-myristate-13-acetate (PMA), and sodium fluoride in a dose-dependent manner[7].
References:
[1]. Toullec D, Pianetti P, Coste H, et al. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771-81. PMID: 1874734.
[2]. Fabre S, Prudhomme M, Rapp M. Protein kinase C inhibitors; structure-activity relationships in K252c-related compounds. Bioorg Med Chem. 1993 Sep;1(3):193-6. doi: 10.1016/s0968-0896(00)82121-5. PMID: 8081852.
[3]. Pajak B, Orzechowska S, Gajkowska B, Orzechowski A. Bisindolylmaleimides in anti-cancer therapy - more than PKC inhibitors. Adv Med Sci. 2008;53(1):21-31. doi: 10.2478/v10039-008-0028-6. PMID: 18635421.
[4]. Silnitsky S, Rubin SJS, Zerihun M, Qvit N. An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases. Int J Mol Sci. 2023 Dec 18;24(24):17600. doi: 10.3390/ijms242417600. PMID: 38139428; PMCID: PMC10743896.
[5].Anderson PW, McGill JB, Tuttle KR. Protein kinase C beta inhibition: the promise for treatment of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2007 Sep;16(5):397-402. doi: 10.1097/MNH.0b013e3281ead025. PMID: 17693752.
[6]. Willems F, Amraoui Z, Vanderheyde N, et al. Expression of c-FLIP(L) and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide. Blood. 2000 Jun 1;95(11):3478-82. PMID: 10828032.
[7]. Krämer HJ, Kessler D, Hipler UC, et al. Pityriarubins, novel highly selective inhibitors of respiratory burst from cultures of the yeast Malassezia furfur: comparison with the bisindolylmaleimide arcyriarubin A. Chembiochem. 2005 Dec;6(12):2290-7. doi: 10.1002/cbic.200500163. PMID: 16252297.
Bisindolylmaleimide IV是一种强效的细胞膜透过性蛋白激酶C(PKC)抑制剂，其IC50值为0.1-0.55μM[1]。Bisindolylmaleimide IV还能抑制cAMP依赖性蛋白激酶(PKA)，其IC50值为3.1-11.8μM[2]。Bisindolylmaleimide IV主要用于癌症生物学[3]、心血管疾病[4]和糖尿病的研究，特别是在研究PKC介导的信号通路及其对细胞功能的影响方面[5]。
Bisindolylmaleimide IV(20μM)可下调细胞型 caspase 8(FLICE)样抑制蛋白(c-FLIPL)的表达，并促进CD95介导的单核细胞来源的树突状细胞凋亡[6]。Bisindolylmaleimide IV(0.1-100μM)能够以剂量依赖的方式抑制由IL-3、佛波醇-12-肉豆蔻酸-13-乙酸酯(PMA)和氟化钠等刺激剂诱导的中性粒细胞活性氧(ROS)释放[7]。