LY 333531 hydrochloride (Synonyms: Ruboxistaurin) |
Catalog No.GC17563
One-Click Copy Product Info
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El clorhidrato de ruboxistaurina (LY333531) es un inhibidor beta selectivo de la PKC activo por vÍa oral (Ki = 2 nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 169939-93-9
Sample solution is provided at 25 µL, 10mM.
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LY 333531 hydrochloride is an orally selective and ATP-competitive PKCβ inhibitor with IC50 values of 4.7nM and 5.9nM for PKCβI and PKCβII, respectively[1]. LY 333531 hydrochloride inhibits Ser180 phosphorylation of Bruton's tyrosine kinase (BTK), with an EC50 value of 0.21μM[2]. By targeting PKCβ, LY 333531 hydrochloride alleviates diastolic dysfunction, myocardial hypertrophy and collagen deposition, and maintains myocardial contractility[3]. LY 333531 hydrochloride has been widely used in diabetic rat models to restore the renal hemodynamic indicators and improve renal function[4].
In vitro, LY 333531 hydrochloride treatment for 24 hours significantly inhibited the proliferation of MOLM13 cells harboring FLT3-ITD mutation (IC50=0.7μM) and induced cell apoptosis (IC50=1.5μM)[5]. Incubation with 1μM of LY 333531 hydrochloride for 48 hours markedly suppressed VEGF (10ng/ml)-induced proliferation and migration of human umbilical vein endothelial cells (HUVECs), and decreased the phosphorylation of ERK1/2 and Akt[6]. Pretreatment with 10nM LY 333531 hydrochloride for 2 hours ameliorated reactive oxygen species (ROS) production, decreased cell permeability, and alleviated oxidative stress in stretch-treated human coronary artery endothelial cells (HCAECs)[7].
In vivo, LY 333531 hydrochloride treatment via oral administration at a dose of 10mg/kg/day for 8 weeks attenuated the increased urinary albumin excretion rate, glomerular volume, and tubulointerstitial injury index in diabetic rats[8]. Oral administration of LY 333531 hydrochloride at a dose of 10mg/kg/day for 4 weeks reduced the number of leukocytes trapped in the retinal microcirculation and ameliorated abnormal retinal blood flow in early diabetic rats[9].
References:[1] Jirousek M R, Gillig J R, Gonzalez C M, et al. (S)-13-[(Dimethylamino) methyl]-10, 11, 14, 15-tetrahydro-4, 9: 16, 21-dimetheno-1 H, 13 H-dibenzo [e, k] pyrrolo [3, 4-h][1, 4, 13] oxadiazacyclohexadecene-1, 3 (2 H)-dione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase Cβ[J]. Journal of medicinal chemistry, 1996, 39(14): 2664-2671.
[2] Venkataraman C, Chen X C, Na S, et al. Selective role of PKCβ enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking[J]. Immunology letters, 2006, 105(1): 83-89.
[3] Connelly K A, Kelly D J, Zhang Y, et al. Inhibition of protein kinase C–β by ruboxistaurin preserves cardiac function and reduces extracellular matrix production in diabetic cardiomyopathy[J]. Circulation: Heart Failure, 2009, 2(2): 129-137.
[4] Koya D, Jirousek M R, Lin Y W, et al. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats[J]. The Journal of clinical investigation, 1997, 100(1): 115-126.
[5] Fedorov O, Marsden B, Pogacic V, et al. A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases[J]. Proceedings of the National Academy of Sciences, 2007, 104(51): 20523-20528.
[6] Nakamura S, Chikaraishi Y, Tsuruma K, et al. Ruboxistaurin, a PKCβ inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt[J]. Experimental eye research, 2010, 90(1): 137-145.
[7] Li X, Wang M, Kalina J O, et al. Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis[J]. Redox biology, 2024, 69: 102979.
[8] Wu Y, Wu G, Qi X, et al. Protein kinase C β inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats[J]. Journal of pharmacological sciences, 2006, 101(4): 335-343.
[9] Nonaka A, Kiryu J, Tsujikawa A, et al. PKC-β inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats[J]. Investigative ophthalmology & visual science, 2000, 41(9): 2702-2706.
| Cell experiment [2]: | |
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Cell lines |
Human umbilical vein endothelial cells (HUVECs) |
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Preparation Method |
Human umbilical vein endothelial cells (HUVECs) were cultivated in endothelial cell medium-2 (EGM-2) supplemented with 2% fetal bovine serum, 10ng/ml recombinant human epidermal growth factor (hEGF), 1μg/ml hydrocortisone, 50μg/ml gentamicin, 50ng/ml amphotericin B, 5ng/ml recombinant human basic fibroblast growth factor-B (hFGF-B) and 10μg/ml heparin at 37°C in an incubator with 5% CO2. HUVECs were thawed and plated in 96-well tissue culture plates at 2000 cells/well for 24h. The cells were treated with different concentration of LY 333531 hydrochloride (0, 0.1, and 1μM) in the presence of 10ng/ml VEGF for 48h. Cell proliferation was measured. |
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Reaction Conditions |
0, 0.1, and 1μM; 48h |
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Applications |
LY 333531 hydrochloride treatment reduced the VEGF-induced cell proliferation of HUVECs in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Male Munich-Wistar rats |
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Preparation Method |
Male Munich-Wistar rats (180-200g) were housed in a specific pathogen-free (SPF) barrier environment and were continuously provided with sterilized food, water, and bedding. All rats were initially subjected to removal of the right kidney under anesthesia with sodium pentobarbital (50mg/kg; i.p.) to hasten the development of diabetic nephropathy, and then rats were rendered diabetic two weeks later by a single injection of streptozotocin at a dose of 65mg/kg (i.p.), diluted in citrate buffer 0.1M (pH 4.0). Two days later, the diabetic state was confirmed by measurement of tail blood glucose (BG) levels using a glucometer. Rats were treated with LY 333531 hydrochloride (10mg/kg per day by oral gavage). LY 333531 hydrochloride was dissolved in the drinking water. After 8 weeks, kidney tissues from rats were collected for analysis. |
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Dosage form |
10mg/kg/day; 8 weeks; p.o. |
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Applications |
LY 333531 hydrochloride treatment attenuated ICAM-1 and MCP-1 protein expression and inhibited PKC activity and PKC-β protein expression in the kidney of diabetic rats. |
| References: [1] Nakamura S, Chikaraishi Y, Tsuruma K, et al. Ruboxistaurin, a PKCβ inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt[J]. Experimental eye research, 2010, 90(1): 137-145. [2] Wu Y, Wu G, Qi X, et al. Protein kinase C β inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats[J]. Journal of pharmacological sciences, 2006, 101(4): 335-343. | |
| Cas No. | 169939-93-9 | SDF | |
| Sinónimos | Ruboxistaurin | ||
| Chemical Name | A name could not be generated for this structure. | ||
| Canonical SMILES | O=C(C1=C2C(C3=CC=CC=C43)=CN4CCO[C@H](CN(C)C)CCN5C6=CC=CC=C6C1=C5)NC2=O.Cl | ||
| Formula | C28H28N4O3.HCl | M.Wt | 505.01 |
| Solubility | DMSO: 10 mg/ml | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9802 mL | 9.9008 mL | 19.8016 mL |
| 5 mM | 396 μL | 1.9802 mL | 3.9603 mL |
| 10 mM | 198 μL | 990.1 μL | 1.9802 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)