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.
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Ruboxistaurin Chemical Structure
CAS No. : 169939-94-0
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Western blots analysis showing protein expression level of phosphorylated p-PKC βII over total PKC βII and total H3Cit over total H3 in wounds 12 days post wounding
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Description
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[1][2].
IC50 & Target[1]
PKC-βI
4.7 nM (IC50)
PKC-βII
5.9 nM (IC50)
PKCη
52 nM (IC50)
PKCδ
250 nM (IC50)
PKCγ
300 nM (IC50)
PKCα
360 nM (IC50)
PKCε
600 nM (IC50)
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)[1]. 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[2]. 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[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Ruboxistaurin Related Antibodies
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[3]. 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[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Rats[4]
Dosage:
0.1, 1.0, or 10.0 mg/kg
Administration:
P.o.
Result:
Dramatically reduced the number of leukocytes trapped in the retinal microcirculation of diabetic rats.
Room temperature in continental US; may vary elsewhere.
Stockage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvant et solubilité
In Vitro:
DMSO : 25 mg/mL (53.36 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
THF : < 1 mg/mL (insoluble)
Preparing Stock Solutions
ConcentrationSolventMass
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
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
This protocol yields a suspended solution of ≥ 1.67 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Jirousek MR, et al. (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem. 1996;39(14):2664-2671.
[Content Brief]
[2]. Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-199.
[Content Brief]
[3]. Kunt T, et al. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of human monocytes to endothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35.
[Content Brief]
[4]. Nonaka A, et al. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2702-6.
[Content Brief]
[1]. Jirousek MR, et al. (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem. 1996;39(14):2664-2671.
[2]. Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-199.
[3]. Kunt T, et al. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of human monocytes to endothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35.
[4]. Nonaka A, et al. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2702-6.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.1342 mL
10.6712 mL
21.3424 mL
53.3561 mL
5 mM
0.4268 mL
2.1342 mL
4.2685 mL
10.6712 mL
10 mM
0.2134 mL
1.0671 mL
2.1342 mL
5.3356 mL
15 mM
0.1423 mL
0.7114 mL
1.4228 mL
3.5571 mL
20 mM
0.1067 mL
0.5336 mL
1.0671 mL
2.6678 mL
25 mM
0.0854 mL
0.4268 mL
0.8537 mL
2.1342 mL
30 mM
0.0711 mL
0.3557 mL
0.7114 mL
1.7785 mL
40 mM
0.0534 mL
0.2668 mL
0.5336 mL
1.3339 mL
50 mM
0.0427 mL
0.2134 mL
0.4268 mL
1.0671 mL
Ruboxistaurin Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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