Description
LY333531 is an inhibitor of PKCβ (IC
50s = 4.7 and 5.9 nM for PKCβ1 and PKCβ2, respectively). It is selective for PKCβ1 and PKCβ2 over PKCα, -γ, -δ, -ε, -ζ, and -η (IC
50s = 360, 300, 250, >100,000, and 52 nM, respectively). LY333531 also inhibits glycogen synthase kinase 3β (GSK3β; IC
50 = 39.4 nM). It inhibits neutrophil extracellular trap (NET) formation induced by phorbol 12-myristate 13-acetate (PMA; ) in primary human neutrophils when used at a concentration of 1 μM. LY333531 increases the mechanical nociceptive threshold in a rat model of diabetic hyperalgesia induced by streptozotocin (STZ; ).
Uses
Ruboxistaurin is a protein kinase C (PKC) β inhibitor, exhibits significant anti-angiogenic activity that reduces the response of vascular endothelial cells to stimulation by vascular endothelial growth factor (VEGF). Ruboxistaurin is used in treatment of diabetic microvascular complications.
Uses
A protein kinase C (PKC) β inhibitor, exhibits significant anti-angiogenic activity that reduces the response of vascular endothelial cells to stimulation by vascular endothelial growth factor (VEGF). It is used in treatment of diabetic microvascular comp
in vivo
Ruboxistaurin (1 mg/kg; 8 weeks) markedly reduces GEC apoptosis as well as swiprosin-1 upregulation, and ameliorates renal glomerular injury in the diabetic mice. Ruboxistaurin also potently attenuates the expression of PARP, cleaved-caspase9, cleaved-caspase3, and the Bax/Bcl-2 ratio, in diabetic mice[3]. Ruboxistaurin (0.1, 1.0, or 10.0 mg/kg; p.o.) dramatically reduces the number of leukocytes trapped in the retinal microcirculation of diabetic rats[4].
IC 50
PKCβI: 4.7 nM (IC
50); PKCβII: 5.9 nM (IC
50); PKCη: 52 nM (IC
50); PKCδ: 250 nM (IC
50); PKCγ: 300 nM (IC
50); PKCα: 360 nM (IC
50); PKCε: 600 nM (IC
50)
References
[1] MICHAEL R. JIROUSEK. (S)-13-[(Dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno- 1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione (LY333531) and Related Analogues: Isozyme Selective Inhibitors of Protein Kinase Cβ[J]. Journal of Medicinal Chemistry, 1996, 39 14: 2664-2671. DOI:
10.1021/jm950588y[2] PATRICIA A. VIGNAUX. Machine Learning for Discovery of GSK3β Inhibitors[J]. ACS Omega, 2020, 5 41: 26551-26561. DOI:
10.1021/acsomega.0c03302[3] ROBERT D GRAY. Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps.[J]. Journal of Inflammation-London, 2013, 10 1: 12. DOI:
10.1186/1476-9255-10-12[4] HYOH KIM. Protein kinase Cbeta selective inhibitor LY333531 attenuates diabetic hyperalgesia through ameliorating cGMP level of dorsal root ganglion neurons.[J]. Diabetes, 2003, 52 8: 2102-2109. DOI:
10.2337/diabetes.52.8.2102
