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5mg |
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10mg |
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Purity: ≥98%
Ruboxistaurin mesylate (LY333531 mesylate), the mesylate salt of Ruboxistaurin, is a potent and specific inhibitor of PKCβ (protein kinase C) with antidiabetic activity. It acts by competitively and reversibly inhibiting PKCβ1 and PKCβ2 with IC50 values of 4.7 and 5.9 nM respectively. It has the usefulness to treat diabetic nephropathy and diabetic macular edem. LY333531 strikingly decreases the chance of HUVEC survival and the effect of LY333531 on apoptotic cell death in HUVEC significantly increases compared with the AGEs group. Blockade of PKC-beta up-regulates the expression of Bax and Bad proteins and down-regulates the expression of Bcl-2 protein. Moreover, LY333531 reduces the ratio of Bcl-2/Bax.
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].
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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].
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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. |
References |
[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. |
Molecular Formula |
C29H32N4O6S
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Molecular Weight |
564.66
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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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SMILES |
S(C)(=O)(=O)O.O1CCN2C=C(C3C=CC=CC2=3)C2C(NC(C=2C2=CN(C3C=CC=CC2=3)CC[C@H]1CN(C)C)=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 |
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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. |
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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. th> |
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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. td> |
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. td> |