| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PKCβ (PKCβI IC50 = 4.7 nM; PKCβII IC50 = 5.9 nM)
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|---|---|
| ln Vitro |
Ruboxistaurin mesylate had IC50 values of 0.36, 0.0047, 0.0059, 0.30, 0.25, 0.60, and 0.052 μM against PKCα, PKCβI, PKCβII, PKCγ, PKCδ, PKCε, and PKCη, respectively [1]. With IC50s of 6.2 and 0.32 μM, respectively, rutosidestatin mesylate inhibits rat brain PKC and calcium calmodulin[1]. In normoglycemic (NG) settings, rutinistaurin mesylate (10 and 400 nM; 4 days) dramatically reduces glucose-induced monocyte adhesion [3].
Ruboxistaurin demonstrates potent inhibition of PKCβ with IC50 values of 4.7 nM and 5.9 nM for PKCβI and PKCβII, respectively. It shows selectivity for PKCβ over other PKC isozymes including PKCα, PKCδ, PKCε, and PKCγ. The mesylate salt form provides improved solubility. In cellular assays, the compound inhibits PKCβ-mediated phosphorylation of downstream substrates and modulates signaling pathways involved in diabetic complications including VEGF expression and vascular permeability. |
| ln Vivo |
In the initial stages of diabetes, rutinistaurin mesylate (0.1, 1.0, and 10.0 mg/kg; orally, once daily for three weeks) inhibits the increase in leukocyte retention in the retinal microcirculation [4].
In vivo, Ruboxistaurin demonstrates efficacy in animal models of diabetic complications. Oral administration results in significant modulation of disease endpoints in a dose-dependent manner, including reduction of retinal vascular permeability, glomerular filtration rate, and improvement in nerve conduction velocity. The compound shows good pharmacokinetic properties with adequate exposure to achieve therapeutic concentrations. |
| Enzyme Assay |
PKCβ kinase activity is measured using radiometric kinase assays with recombinant PKCβ enzyme and appropriate peptide substrates. IC50 values are determined from dose-response curves. Selectivity profiling is conducted against other PKC isozymes and other kinases to establish the selectivity profile. Binding affinity is assessed using competition binding assays.
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| Cell Assay |
Cellular potency is evaluated in vascular endothelial cells, renal cells, and neuronal cells by measuring PKCβ-mediated phosphorylation using Western blot. VEGF-induced signaling and vascular permeability are assessed. Effects on cellular function relevant to diabetic complications are measured to characterize the compound's activity.
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| Animal Protocol |
Animal/Disease Models: Male long-evans rats with streptozotocin induced diabetes[4]
Doses: 0.1, 1.0 and 10.0 mg/kg Route of Administration: Oral administration; 0.1, 1.0 and 10.0 mg/kg, one time/day for 4 weeks Experimental Results: Dramatically diminished the number of leukocytes in the retinal microcirculation of rats with streptozotocin induced diabetes. In vivo efficacy is evaluated in animal models of diabetes including streptozotocin-induced diabetic rats and db/db mice. Ruboxistaurin is administered orally at various doses. Retinal vascular permeability, renal function, and nerve conduction velocity are measured. Pharmacodynamic biomarkers including PKCβ phosphorylation are assessed in target tissues. |
| ADME/Pharmacokinetics |
Ruboxistaurin demonstrates favorable pharmacokinetic properties with good oral bioavailability and adequate half-life for once-daily or twice-daily dosing. The compound shows acceptable clearance and volume of distribution. Detailed PK parameters including Cmax, AUC, half-life, and bioavailability are available from clinical studies. The compound is a substrate for relevant metabolic enzymes.
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| Toxicity/Toxicokinetics |
Ruboxistaurin has been evaluated in extensive clinical trials for diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Safety data from these trials indicate that the compound is generally well-tolerated at therapeutic doses. Comprehensive toxicology data are available from the clinical development program. Some Phase 3 trials did not meet primary endpoints, leading to development discontinuation.
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| References | |
| Additional Infomation |
Ruboxistaurin (LY333531) mesylate was developed by Eli Lilly as a PKCβ inhibitor for diabetic complications. Despite showing efficacy in preclinical models and Phase 2 trials, Phase 3 studies did not consistently meet primary endpoints, and development was discontinued. The compound remains a valuable research tool for studying PKCβ biology and diabetic complications.
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| Molecular Formula |
C29H32N4O6S
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|---|---|
| Molecular Weight |
564.66
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| Exact Mass |
564.204
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| CAS # |
192050-59-2
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| Related CAS # |
Ruboxistaurin;169939-94-0;Ruboxistaurin hydrochloride;169939-93-9
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| PubChem CID |
11577725
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| Appearance |
Orange to red solid powder
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| LogP |
4.374
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
40
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| Complexity |
965
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN(C)C[C@@H]1CCN2C=C(C3=CC=CC=C32)C4=C(C5=CN(CCO1)C6=CC=CC=C65)C(=O)NC4=O.CS(=O)(=O)O
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| InChi Key |
DUHQBKLTAVUXFF-FERBBOLQSA-N
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| InChi Code |
InChI=1S/C28H28N4O3.CH4O3S/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;1-5(2,3)4/h3-10,16-18H,11-15H2,1-2H3,(H,29,33,34);1H3,(H,2,3,4)/t18-;/m0./s1
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| Chemical Name |
(9S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione mesylate
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| Synonyms |
LY-333531 Mesylate; LY333531; Ruboxistaurin mesylate; 192050-59-2; Ruboxistaurin mesilate; UNII-6V860VW8AO; 6V860VW8AO; Ruboxistaurin mesylate; LY-333531; LY 333531; LY-333531 Mesylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7710 mL | 8.8549 mL | 17.7098 mL | |
| 5 mM | 0.3542 mL | 1.7710 mL | 3.5420 mL | |
| 10 mM | 0.1771 mL | 0.8855 mL | 1.7710 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Effects of PKCβ inhibitor (LY333531) treatment upon subcellular distributions of PKCβ1and PKCβ2and expression levels of Cav-1 and Cav-3 in total heart preparations and various isolated cellular fractions.Diabetes. 2013 Jul; 62(7): 2318–2328. |
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Effects of PKCβ inhibitor (LY333531) treatment upon the levels of NO, O2−, nitrotyrosine, and protein expression of p-Akt, p-eNOS, and iNOS in diabetic myocardium.Diabetes. 2013 Jul; 62(7): 2318–2328. |
Expression of p-PKCβ2and Cav-3 in cultured cardiomyocytes and H9C2 cells after various treatments in LG (5.5 mmol/L) or HG (25 mmol/L) conditions for 36 h.Diabetes. 2013 Jul; 62(7): 2318–2328. |
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