Ruboxistaurin hydrochloride

SKU: orb1225962

Description

A potent, selective, ATP-competitive, orally available PKC beta (PKCβ) inhibitor with IC50 of 4.7 and 5.9 nM for PKCβ I and PKCβ II, respectively; displays >60-fold selectivity over PKCα, and other ATP dependent kinases (PKA, Calcium calmodulin, Caesin kinase and Src); ameliorates the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats.Heart Failure Phase 2 Discontinued.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 169939-93-9
• MW: 505.0079
• Purity: >98% (HPLC)
• Formula: C₂₈H₂₉ClN₄O₃
• SMILES: CN(C)CC1CCN2C=C(C3=CC=CC=C32)C4=C(C5=CN(CCO1)C6=CC=CC=C65)C(=O)NC4=O.Cl
• Target: PKC
• Solubility: DMSO: 6.8 mg/mL (Need ultrasonic and warming)

Bioactivity

• 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. 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.
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• In Vitro:
  Ruboxistaurin hydrochloride is a selective and ATP-competitive PKCβ inhibitor, with IC50s of 4.7 and 5.9 nM for PKCβI and PKCβII, shows less potent inhibition on PKCη (IC50, 52 nM), PKCα (IC50, 360 nM), PKCγ (IC50, 300 nM), PKCδ (IC50, 250 nM), and has no effect on PKCζ (IC50, >100 μM). Ruboxistaurin (10 and 400 nM) dramatically inhibits glucose-induced monocyte adherence to levels that are not different from baseline adherence of monocytes to endothelial cells under NG conditions. Ruboxistaurin (10 and 400 nM) dose not alter the endothelial expression of adhesion molecules or modify endothelial cell growth. Ruboxistaurin (LY333531; 10 nM) reduces high-glucose (HG)-induced human renal glomerular endothelial cells (HRGECs) viability, and inhibits the increases in swiprosin-1 in HRGECs incubated with HG.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY333531 hydrochloride | LY-333531 hydrochloride

Quick Database Links

Gene Symbol

PKC