| Size | Price | Stock | Qty |
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| Other Sizes |
Purity: ≥98%
| Targets |
The primary target of Ruboxistaurin is protein kinase C beta (PKCβ), a serine/threonine protein kinase that is a member of the PKC family. PKCβ is involved in various cellular processes, including cell growth, differentiation, and apoptosis, and is activated by diacylglycerol and calcium. Ruboxistaurin acts as a selective, ATP-competitive inhibitor of PKCβ, with a Ki of 2 nM. It inhibits PKCβ I with an IC50 of 4.7 nM. By inhibiting PKCβ, Ruboxistaurin modulates downstream signaling pathways involved in diabetic complications.
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| ln Vitro |
Ruboxistaurin is a PKCβ benchmark that is both selective and ATP-competitive. Its IC50s for PKCβI and PKCβII are 4.7 and 5.9 nM, respectively. It also exhibits modest inhibition of PKCη (IC50: 52 nM), PKCα (IC50: 360 nM), PKCγ (IC50: 300 nM), and PKCδ (IC50: 250 nM). It has no effect on PKC z (IC50: >100 μM). Significantly inhibiting pivoted monocyte apoptosis at concentrations indistinguishable from near labeling of endothelial cells by monocytes under NG circumstances was ruboxistaurin (10 and 400 nM). Both endothelial cell proliferation and marker molecule expression are unaffected by rutobistatin (10 and 400 nM) [2]. Human glomerular endothelial (HRGEC) vitality induced by high gradients (HG) is decreased by rutosistaurin (LY333531; 10 nM), which also prevents the increase in swiprosin-1 in HRGEC with HG [3].
Ruboxistaurin demonstrates potent and selective inhibition of PKCβ in vitro, with a Ki of 2 nM and an IC50 of 4.7 nM for PKCβ I. The compound acts as an ATP-competitive inhibitor, meaning it competes with ATP for binding to the kinase active site. However, detailed cellular activity data, such as effects on PKCβ-mediated signaling pathways, are not extensively reported in the available literature. |
| ln Vivo |
In diabetic mice, ruboxistaurin (1 mg/kg; 8 weeks) dramatically decreased the overexpression of swiprosin-1 and GEC while also improving glomerular damage. Ruboxistaurin has the ability to efficiently inhibit the expression of PARP, cleaved-caspase9, cleaved-caspase3, and Bax/Bcl-2 in diabetic mice [3]. The oral dose of rutinistaurin (0.1–10.0 mg/kg) dramatically lowers the amount of leukocytes in the diabetic microcirculation [4].
Ruboxistaurin has been investigated in clinical trials for the treatment of diabetic complications, including diabetic retinopathy and diabetic nephropathy. The compound is orally active, indicating good oral bioavailability. However, specific in vivo efficacy data, including clinical trial results, are not extensively detailed in the available literature. |
| Enzyme Assay |
In vitro enzyme assays for Ruboxistaurin typically involve measuring its inhibition of PKCβ activity. Recombinant PKCβ enzyme is incubated with a peptide substrate and ATP in the presence of varying concentrations of Ruboxistaurin. The incorporation of phosphate into the substrate is measured, and the IC50 for inhibition is calculated. Ruboxistaurin shows an IC50 of 4.7 nM for PKCβ I. The Ki of 2 nM is determined from enzyme kinetics at different ATP concentrations.
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| Cell Assay |
Cellular assays for Ruboxistaurin are performed in cells to assess its effects on PKCβ-mediated signaling. Cells are treated with Ruboxistaurin, and the phosphorylation of PKCβ substrates is measured by Western blotting using phospho-specific antibodies. The compound's effects on cell proliferation, apoptosis, and other PKCβ-dependent processes are assessed.
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| Animal Protocol |
Animal/Disease Models: Rat[4]
Doses: 0.1, 1.0 or 10.0 mg/kg Route of Administration: Po Experimental Results: Dramatically diminished the number of leukocytes retained in the retinal microcirculation of diabetic rats. In vivo animal studies with Ruboxistaurin have been performed in models of diabetic complications. In these studies, Ruboxistaurin is administered orally, and its effects on diabetic retinopathy, nephropathy, and other complications are assessed. The compound's efficacy in these models supports its potential for the treatment of diabetic complications. However, specific protocols are not extensively detailed in the available literature. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Ruboxistaurin's known human metabolites include N-demethyl LY333531. Ruboxistaurin has a molecular weight of 468.5. It is orally active, indicating good oral bioavailability. The compound is soluble in DMSO and other organic solvents. However, detailed pharmacokinetic parameters such as absorption, distribution, metabolism, excretion, half-life, and bioavailability are not extensively reported in the available literature. |
| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Ruboxistaurin are not extensively reported. As a compound that has been investigated in clinical trials, it would have undergone toxicological evaluation, but specific data are not detailed in the available literature. The compound is classified as a research-use-only chemical and is not intended for human consumption.
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| References | |
| Additional Infomation |
Rubostalin has been used in basic science research on type 2 and type 1 diabetes.
Ruboxistaurin is a research-grade compound that has been investigated in clinical trials for the treatment of diabetic complications, including diabetic retinopathy and diabetic nephropathy. It is a selective, orally active inhibitor of PKCβ. The compound's primary application is as a pharmacological tool for studying the role of PKCβ in various diseases. Its selectivity for PKCβ makes it a valuable tool for dissecting PKCβ-mediated signaling pathways. |
| Molecular Formula |
C28H28N4O3
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|---|---|
| Molecular Weight |
468.55
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| Exact Mass |
468.216
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| CAS # |
169939-94-0
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| Related CAS # |
Ruboxistaurin mesylate;192050-59-2;Ruboxistaurin hydrochloride;169939-93-9
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| PubChem CID |
153999
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| Appearance |
Brown to reddish brown solid powder
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| Density |
1.34g/cm3
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| Boiling Point |
744.4ºC at 760mmHg
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| Flash Point |
404ºC
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| Vapour Pressure |
4.93E-22mmHg at 25°C
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| Index of Refraction |
1.695
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| LogP |
3.789
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
35
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| Complexity |
872
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN(C[C@@H]1CCN2C=C(C3=C(C(NC3=O)=O)C4=CN(C5=CC=CC=C45)CCO1)C6=CC=CC=C62)C
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| InChi Key |
ZCBUQCWBWNUWSU-SFHVURJKSA-N
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| InChi Code |
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
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| 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
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| Synonyms |
LY-333531 LY333531 LY 333531
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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 |
| 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) |
DMSO : ~25 mg/mL (~53.36 mM)
THF :< 1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1342 mL | 10.6712 mL | 21.3424 mL | |
| 5 mM | 0.4268 mL | 2.1342 mL | 4.2685 mL | |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1342 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02769611 | WITHDRAWN | Drug: Ruboxistaurin | Heart Failure | University of Tennessee | 2017-06-28 | Phase 1 Phase 2 |
| NCT00190970 | COMPLETED | Drug: Ruboxistaurin | Diabetic Neuropathy | Chromaderm, Inc. | 2004-10 | Phase 2 |
| NCT00133952 | COMPLETEDWITH RESULTS | Drug: Ruboxistaurin Drug: Placebo |
Diabetic Macular Edema | Chromaderm, Inc. | 2005-08 | Phase 3 |
| NCT00266695 | COMPLETEDWITH RESULTS | Drug: Ruboxistaurin | Diabetic Retinopathy | Chromaderm, Inc. | 2006-01 | Phase 3 |
| NCT00297401 | COMPLETED | Drug: ruboxistaurin Drug: placebo |
Diabetes Mellitus, Type 1 | Chromaderm, Inc. | 2006-03 | Phase 3 |
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