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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H28N4O3.CH4O3S.H2O
Molecular Weight 582.6701
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RUBOXISTAURIN MESYLATE MONOHYDRATE

SMILES

CN(C)C[C@]1([H])CCn2cc(c3ccccc32)C4=C(c5cn(CCO1)c6ccccc56)C(=O)N=C4O.CS(=O)(=O)O.O

InChI

InChIKey=YTKBKIVYPITVAO-NTEVMMBTSA-N
InChI=1S/C28H28N4O3.CH4O3S.H2O/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);1H2/t18-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.1068
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C28H28N4O3
Molecular Weight 468.548
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/23404115 | https://www.ncbi.nlm.nih.gov/pubmed/19825373 | https://www.ncbi.nlm.nih.gov/pubmed/15380221

Ruboxistaurin is an orally bioavailable, selective, potent inhibitor of protein kinase C β developed for treating diabetic retinopathy. In vitro and in vivo non-clinical models have demonstrated that Ruboxistaurin decreases PKC β activity and ameliorates many of the effects of PKC β on pathologic processes in the retina. Ruboxistaurin prevents the slowing of retinal blood flow that is observed by fluorescein video angiography in the eyes of diabetic rats. It is also reported to cause regression of retinal neovascularization produced by laser-induced major branch vein occlusions in a porcine model. Ruboxistaurin positively affected the diabetes-induced retinal blood flow abnormalities in a Phase Ib study in diabetic patients. Ruboxistaurin is in phase III clinical trials for the treatment of diabetic nephropathy and diabetic macular edema. Eli Lilly had submitted Ruboxistaurin for approval in the US and the EU; however, the company subsequently discontinued development as it was unable to demonstrate sufficient efficacy

Approval Year

PubMed

PubMed

TitleDatePubMed
(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.
1996 Jul 5
Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors.
2004 Oct 18
Inhibition of PKC beta by ruboxistaurin does not enhance the acute blood pressure response to nitroglycerin.
2007 Aug
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
2007 Dec 18
Protein kinase C beta inhibitors: a new therapeutic target for diabetic nephropathy and vascular complications.
2008 Jun
Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach.
2009 Jul 17
Selective inhibition of protein kinase C beta(2) attenuates inducible nitric oxide synthase-mediated cardiovascular abnormalities in streptozotocin-induced diabetic rats.
2009 Oct
Inhibition of protein kinase Cbeta does not improve endothelial function in type 2 diabetes.
2010 Aug
Blockade of PKC-beta protects HUVEC from advanced glycation end products induced inflammation.
2010 Dec
A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats.
2010 Jul
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Docetaxel Facilitates Endothelial Dysfunction through Oxidative Stress via Modulation of Protein Kinase C Beta: The Protective Effects of Sotrastaurin.
2015 May
Patents

Patents

Sample Use Guides

32 mg/day
Route of Administration: Oral
HUVECs co-cultured with fibroblasts were cultivated in the presence or absence of various concentrations of ruboxistaurin (0.1 and 1 mkM) plus VEGF (10 ng/ml) at days 1, 4, 7 and 9. The ruboxistaurin was dissolved in dimethyl sulfoxide (DMSO, final concentration of DMSO was 0.1%). DMSO (0.1%) was added to the non-drug control (control group). At day 11, cells were fixed in 70% ethanol. The cells were incubated with diluted primary antibody (mouse anti-human CD31, 1 : 4000) for 1 h at 37 C, and with the secondary antibody (goat anti-mouse IgG alkaline phosphataseconjugated antibody, 1 : 500) for 1 h at 37 C. Visualization was achieved using 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium.
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:13:22 UTC 2021
Edited
by admin
on Fri Jun 25 23:13:22 UTC 2021
Record UNII
4TY24FTS56
Record Status Validated (UNII)
Record Version
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Name Type Language
RUBOXISTAURIN MESYLATE MONOHYDRATE
Common Name English
9H,18H-5,21:12,17-DIMETHENODIBENZO(E,K)PYRROLO(3,4-H)(1,4,13)OXADIAZACYCLOHEXADECINE-18,20(19H)-DIONE, 9-((DIMETHYLAMINO)METHYL)-6,7,10,11-TETRAHYDRO-, (9S)-, METHANESULFONATE, HYDRATE (1:1:1)
Common Name English
ARXXANT
Brand Name English
RUBOXISTAURIN METHANESULFONATE MONOHYDRATE [MI]
Common Name English
9H,18H-5,21:12,17-DIMETHENODIBENZO(E,K)PYRROLO(3,4-H)(1,4,13)OXADIAZACYCLOHEXADECINE-18,20(19H)-DIONE, 9-((DIMETHYLAMINO)METHYL)-6,7,10,11-TETRAHYDRO-, (9S)-, MONOMETHANESULFONATE, MONOHYDRATE
Systematic Name English
RUBOXISTAURIN METHANESULFONATE MONOHYDRATE
MI  
Common Name English
Code System Code Type Description
PUBCHEM
6918370
Created by admin on Fri Jun 25 23:13:22 UTC 2021 , Edited by admin on Fri Jun 25 23:13:22 UTC 2021
PRIMARY
MERCK INDEX
M9693
Created by admin on Fri Jun 25 23:13:22 UTC 2021 , Edited by admin on Fri Jun 25 23:13:22 UTC 2021
PRIMARY Merck Index
FDA UNII
4TY24FTS56
Created by admin on Fri Jun 25 23:13:22 UTC 2021 , Edited by admin on Fri Jun 25 23:13:22 UTC 2021
PRIMARY
CAS
202260-21-7
Created by admin on Fri Jun 25 23:13:22 UTC 2021 , Edited by admin on Fri Jun 25 23:13:22 UTC 2021
PRIMARY
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