Ruboxistaurin hydrochloride

Ruboxistaurin hydrochloride, also known as LY-333531 hydrochloride, is a PKC beta inhibitor potentially for the treatment of diabetic nephropathy and diabetic macular edema. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.

Product information

CAS Number: 169939-93-9

Molecular Weight: 505.01

Formula: C28H29ClN4O3

Synonym:

Ruboxistaurin hydrochloride

LY-333531

Ruboxistaurin

LY333531

LY 333531

Related CAS Number:

169939-94-0 (free base)

202260-21-7 (mesylate hydrate)

192050-59-2 (mesylate)

Chemical Name: (12E,32E,7S)-7-((dimethylamino)methyl)-22,25-dihydro-11H,21H,31H-6-oxa-1,3(3,1)-diindola-2(3,4)-pyrrolacyclononaphane-22,25-dione hydrochloride

Smiles: Cl.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: NYQIEYDJYFVLPO-FERBBOLQSA-N

InChi: InChI=1S/C28H28N4O3.ClH/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);1H/t18-;/m0./s1

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO

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 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.

In Vivo:

Ruboxistaurin hydrochloride (LY333531 hydrochloride; 1 mg/kg/d for 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 (LY333531; 0.1, 1.0, or 10.0 mg/kg/d, po.o.) dramatically reduces the number of leukocytes trapped in the retinal microcirculation of diabetic rats.

References:

1. Pang C, Wen L, Lu X, Luo S, Qin H, Zhang X, Zhu B, Luo S. Ruboxistaurin maintains the bone mass of subchondral bone for blunting osteoarthritis progression by inhibition of osteoclastogenesis and bone resorption activity. Biomed Pharmacother. 2020 Sep 1;131:110650. doi: 10.1016/j.biopha.2020.110650. Epub ahead of print. PMID: 32882584.
2. Zestos AG, Carpenter C, Kim Y, Low MJ, Kennedy RT, Gnegy ME. Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity. ACS Chem Neurosci. 2019 Apr 17;10(4):1960-1969. doi: 10.1021/acschemneuro.8b00259. Epub 2018 Nov 8. PMID: 30384585; PMCID: PMC6470047.
3. Al-Onazi AS, Al-Rasheed NM, Attia HA, Al-Rasheed NM, Ahmed RM, Al-Amin MA, Poizat C. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. J Pharm Pharmacol. 2016 Feb;68(2):219-32. doi: 10.1111/jphp.12504. Epub 2016 Jan 28. PMID: 26817709.

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