Ruboxistaurin (LY333531) HCl

Name: Ruboxistaurin (LY333531) HCl
Brand: Selleck Chemicals
SKU: S7663
Rating: 5 (9 reviews)

For research use only.

Catalog No.S7663 Synonyms: Ruboxistaurin hydrochloride, LY333531 hydrochloride

9 publications

Ruboxistaurin (LY333531) HCl Chemical Structure

CAS No. 169939-93-9

Ruboxistaurin (LY333531) HCl is a β-specific protein kinase C inhibitor. It competitively and reversibly inhibits PKCβ1 and PKCβ2 with IC50 values of 4.7 and 5.9 nM respectively.

Selleck's Ruboxistaurin (LY333531) HCl has been cited by 9 publications

Cell, 2020, 182(3):685-712.e19

PubMed: 32645325 ( click the link to review the publication )

Nat Commun, 2021, 12(1):3493

PubMed: 34108467 ( click the link to review the publication )

Cell Death Dis, 2020, 11(11):953

PubMed: 33159035 ( click the link to review the publication )

Biomed Pharmacother, 2020, 131:110650

PubMed: 32882584 ( click the link to review the publication )

J Ethnopharmacol, 2020, S0378-8741(20)33349-3

PubMed: 33049347 ( click the link to review the publication )

J Clin Invest, 2019, 10.1172/JCI130730

PubMed: 31639107 ( click the link to review the publication )

PLoS One, 2019, 14(3):e0211309

PubMed: 30921339 ( click the link to review the publication )

Cardiovasc Pathol, 2019, 41:11-17

PubMed: 31004933 ( click the link to review the publication )

FEBS Lett, 2014, 588(18):3409-16

PubMed: 25117453 ( click the link to review the publication )

Purity & Quality Control

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Biological Activity

Description

Ruboxistaurin (LY333531) HCl is a β-specific protein kinase C inhibitor. It competitively and reversibly inhibits PKCβ1 and PKCβ2 with IC50 values of 4.7 and 5.9 nM respectively.

Targets

PKCβ1 ^[1] (Cell-free assay)	PKCβ2 ^[1] (Cell-free assay)	PKCη ^[1] (Cell-free assay)	PKCδ ^[1] (Cell-free assay)	PKCγ ^[1] (Cell-free assay)	View More
4.7 nM	5.9 nM	0.052 μM	0.25 μM	0.3 μM	View More

In vitro

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. LY333531 can further prompt AGEs-induced endothelial cells apoptosis. The increased expression of Bax, Bad and decreased expression of Bcl-2 and Bcl-2/Bax ratio are associated with the apoptotic process^[3].

Cell Data

Cell Lines	Assay Type	Concentration	Activity Description	PMID
MOLM13	NFjnTXZCeG:ydH;zbZMh[XO\|YYm=		MmiyTY5lfWO2aX;uJI9nKGGyb4D0c5NqeyCrbjDoeY1idiCPT1zNNVMh[2WubIOsJGlEPTB;MD63JO69VQ>?	NUfVWJdMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwO\|c{PjNpPkG4NFc4OzZ\|PD;hQi=>
MV4-11	NFj0O3JCeG:ydH;zbZMh[XO\|YYm=		NV;xcml2UW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDNWlQuOTFiY3XscJMtKEmFNU2xMlUh\|ryP	MmXPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyN{ezOlMoRjF6MEe3N\|Y{RC:jPh?=
endothelial cells	M1HVNWZ2dmO2aX;uJIF{e2G7		M1TIe2Vn\mWldHn2[UBld3OnIHHnZYlve3RicHzhd41qdm:pZX6gZYN1cX[jdH;yJIFkfGm4aYT5JJN1cW23bHH0[YQh[nlicHjvdoJwdCCnc4TldkBqdiCnbnTveIhmdGmjbDDj[YxteyxiRVS1NF04NjYQvF2=	NEfNVYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi96N{C5NFk2Lz56N{C5NFk2RC:jPh?=
MV4-11	MXfGeY5kfGmxbjDhd5NigQ>?	MWKxJJVO	MkDSVoVlfWO2aX;uJI9nKEKDRDDwbI9{eGixconsZZRqd25iaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF1KDFidV2gZpkhX2W\|dHXyckBjdG:2	NV[5WG5ORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwO\|c{PjNpPkG4NFc4OzZ\|PD;hQi=>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-AMPKα1 / AMPKα1 / p-MARCKS ; PubMed: 27784766 Biochem J HUVECs were pre-treated with the indicated concentrations of LY333531 for 1 h prior to stimulation with VEGF (10 ng/ml, 5 min) or PMA (1 µmol/l, 20 min). Cell lysates were prepared and analysed by immunoblotting with the antibodies indicated.	27784766

In vivo

LY333531 treatment (for a duration of 4 weeks) prevents excessive PKCb2 activation and attenuates cardiac diastolic dysfunction in rats with streptozotocin-induced diabetes. LY333531 suppresses the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigates the augmentation of O2-, nitrotyrosine, Cav-1, and iNOS expression^[2].

Protocol

Cell Research:^[3]

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Cell lines: Human umbilical vein endothelial cell (HUVEC)
Concentrations: 200 nM
Incubation Time: 48 h
Method: HUVECs are seeded into 96-well plates in low glucose DMEM with 10% FBS for 12 h. Afterwards, HUVECs are starved for 12 h and incubated with BSA (200 μg/ml), AGEs (200 μg/ml) and LY333531 (200 nM)+AGEs (200 μg/ml) for 48 h. Then, the medium is replaced with 0.5 mg/ml MTT and at 37 ◦C in a 95% air/5% CO2 incubator for 4 h. Finally, the medium containing MTT is aspirated and replaced by dimethyl sulphoxide (DMSO). OD is measured with a Microplate spectrophotometer. AGEs:advanced glycation end products.
(Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	50 mg/mL (99.0 mM)
	Water	Insoluble
	Ethanol	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Ruboxistaurin (LY333531) HCl SDF

Molecular Weight	505.01
Formula	C₂₈H₂₈N₄O₃.HCl
CAS No.	169939-93-9
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	Ruboxistaurin hydrochloride, LY333531 hydrochloride
Smiles	CN(C)CC1CCN2C=C(C3=CC=CC=C32)C4=C(C5=CN(CCO1)C6=CC=CC=C65)C(=O)NC4=O.Cl

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00297401	Completed	Drug: ruboxistaurin\|Drug: placebo	Diabetes Mellitus Type 1	Chromaderm Inc.\|Heart and Stroke Foundation of Canada	March 2006	Phase 3
NCT00190970	Completed	Drug: Ruboxistaurin	Diabetic Neuropathy	Chromaderm Inc.	October 2004	Phase 2
NCT00482976	Completed	Drug: Ruboxistaurin\|Drug: Placebo	Diabetes Mellitus	Chromaderm Inc.\|Joslin Diabetes Center	December 2003	Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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PKC Signaling Pathway Map

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Ruboxistaurin (LY333531) HCl