Ruboxistaurin

Ruboxistaurin (LY333531) is an orally active, selective PKC beta inhibitor (Ki=2 nM). Ruboxistaurin exhibits ATP dependent competitive inhibition of PKC beta I with an IC50 of 4.7 nM. Ruboxistaurin inhibits PKC beta II with an IC50 of 5.9 nM.

Product information

CAS Number: 169939-94-0

Molecular Weight: 468.55

Formula: C28H28N4O3

Chemical Name: (18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1⁷,¹⁴.0²,⁶.0⁸,¹³.0²²,²⁷]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione

Smiles: CN(C)C[C@@H]1CCN2C=C(C3=C(C4=CN(CCO1)C1=CC=CC=C14)C(=O)NC3=O)C1=CC=CC=C21

InChiKey: ZCBUQCWBWNUWSU-SFHVURJKSA-N

InChi: InChI=1S/C28H28N4O3/c1-30(2)15-18-11-12-31-16-21(19-7-3-5-9-23(19)31)25-26(28(34)29-27(25)33)22-17-32(13-14-35-18)24-10-6-4-8-20(22)24/h3-10,16-18H,11-15H2,1-2H3,(H,29,33,34)/t18-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 50 mg/mL (106.71 mM; ultrasonic and warming and heat to 60°C).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Ruboxistaurin 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.

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.

Products are for research use only. Not for human use.