Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C28H28N4O3.CH4O3S.H2O |
| Molecular Weight | 582.668 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.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=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
| 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 |
| 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 |
| 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 |
DescriptionCurator'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
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
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL3045 |
5.9 nM [IC50] | ||
Target ID: CHEMBL299 |
360.0 nM [IC50] | ||
Target ID: CHEMBL2938 |
300.0 nM [IC50] | ||
Target ID: CHEMBL3616 |
52.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| (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 |
|
| 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
Sample Use Guides
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
Edited
Fri Dec 15 15:58:54 GMT 2023
by
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on
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| Record UNII |
4TY24FTS56
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| Record Status |
Validated (UNII)
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| Record Version |
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m9693
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300000025071
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202260-21-7
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| Related Record | Type | Details | ||
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ANHYDROUS->SOLVATE | |||
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PARENT -> SALT/SOLVATE |
