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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H28N4O3
Molecular Weight 468.548
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RUBOXISTAURIN

SMILES

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

InChI

InChIKey=ZCBUQCWBWNUWSU-SFHVURJKSA-N
InChI=1S/C28H28N4O3/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/h3-10,16-18H,11-15H2,1-2H3,(H,29,33,34)/t18-/m0/s1

HIDE SMILES / InChI

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

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
(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 23:00:43 UTC 2021
Edited
by admin
on Fri Jun 25 23:00:43 UTC 2021
Record UNII
721809WQCP
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RUBOXISTAURIN
INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
RUBOXISTAURIN [WHO-DD]
Common Name English
RUBOXISTAURIN [MI]
Common Name English
RUBOXISTAURIN [INN]
Common Name English
RUBOXISTAURIN [VANDF]
Common Name English
RUBOXISTAURIN [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2089
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
Code System Code Type Description
WIKIPEDIA
RUBOXISTAURIN
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
NCI_THESAURUS
C66524
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
PUBCHEM
153999
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
FDA UNII
721809WQCP
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
DRUG CENTRAL
3533
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
MERCK INDEX
M9693
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY Merck Index
MESH
C099154
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
INN
8108
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL91829
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
CAS
169939-94-0
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
EPA CompTox
169939-94-0
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
DRUG BANK
DB11829
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
EVMPD
SUB25202
Created by admin on Fri Jun 25 23:00:43 UTC 2021 , Edited by admin on Fri Jun 25 23:00:43 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION