| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Ruboxistaurin (LY-333531; LY333531) is a novel, potent and specific inhibitor of PKCβ (protein kinase C) with potential antidiabetic activity. It competitively and reversibly inhibits 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 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].
|
|---|---|
| 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].
|
| 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. |
| 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 |
C28H28N4O3
|
|---|---|
| Molecular Weight |
468.55
|
| CAS # |
169939-94-0
|
| Related CAS # |
Ruboxistaurin mesylate;192050-59-2;Ruboxistaurin hydrochloride;169939-93-9
|
| 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
|
| 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
|
| Synonyms |
LY-333531 LY333531 LY 333531
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~53.36 mM)
THF :< 1 mg/mL |
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA