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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H28N4O3.CH4O3S
Molecular Weight 564.653
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RUBOXISTAURIN MESYLATE

SMILES

CS(O)(=O)=O.CN(C)C[C@@H]1CCN2C=C(C3=C2C=CC=C3)C4=C(C(=O)NC4=O)C5=CN(CCO1)C6=C5C=CC=C6

InChI

InChIKey=DUHQBKLTAVUXFF-FERBBOLQSA-N
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

HIDE SMILES / InChI

Molecular Formula C28H28N4O3
Molecular Weight 468.5469
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including 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

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.9 nM [IC50]
360.0 nM [IC50]
300.0 nM [IC50]
52.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
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
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 Dec 15 15:47:21 UTC 2023
Edited
by admin
on Fri Dec 15 15:47:21 UTC 2023
Record UNII
6V860VW8AO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RUBOXISTAURIN MESYLATE
Common Name English
Ruboxistaurin mesilate [WHO-DD]
Common Name English
RUBOXISTAURIN MESILATE
WHO-DD  
Common Name English
RUBOXISTAURIN METHANESULFONATE ANHYDROUS [MI]
Common Name English
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, METHANESULFONATE, (9S)-
Common Name English
Code System Code Type Description
SMS_ID
100000089588
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
CAS
192050-59-2
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
MERCK INDEX
m9693
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
FDA UNII
6V860VW8AO
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
PUBCHEM
11577725
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
DRUG BANK
DBSALT002088
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
EPA CompTox
DTXSID10172762
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
EVMPD
SUB22089
Created by admin on Fri Dec 15 15:47:21 UTC 2023 , Edited by admin on Fri Dec 15 15:47:21 UTC 2023
PRIMARY
Related Record Type Details
SOLVATE->ANHYDROUS
PARENT -> SALT/SOLVATE