RUBOXISTAURIN MESYLATE MONOHYDRATE

Investigational

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

Structure of RUBOXISTAURIN MESYLATE MONOHYDRATE

Structure Search

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

HIDE SMILES / InChI

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	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
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500068826.pdf
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	Potency
Protein kinase C beta 22 Target ID: CHEMBL3045 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15380221	Inhibitor 8504	5.9 nM [IC50]
Protein kinase C alpha 21 Target ID: CHEMBL299 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12954055	Inhibitor 8504	360.0 nM [IC50]
Protein kinase C gamma 7 Target ID: CHEMBL2938 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12954055	Inhibitor 8504	300.0 nM [IC50]
Protein kinase C eta 10 Target ID: CHEMBL3616 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12749884	Inhibitor 8504	52.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Diabetic retinopathy 17 Sources: https://clinicaltrials.gov/ct2/show/NCT00090519	Primary	Phase III 665	Unknown Approved Use Unknown
Diabetic macular edema 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00133952	Primary	Phase III 665	Unknown Approved Use Unknown
Type 1 diabetes mellitus 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00297401	Primary	Phase III 665	Unknown Approved Use Unknown
Diabetic neuropathy 23 Sources: https://clinicaltrials.gov/ct2/show/NCT00190970	Primary	Phase II 1147	Unknown Approved Use Unknown
Type 2 diabetes mellitus 262 Sources: https://clinicaltrials.gov/ct2/show/NCT00761852	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
204 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16896067/	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
200 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16433874	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
1410 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16896067/	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1364 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16433874	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16896067/	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
13.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16433874	64 mg single, oral dose: 64 mg route of administration: Oral experiment type: SINGLE co-administered:		RUBOXISTAURIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AQSO	https://www.1pchem.com/search?query=1P00AQSO
AChemBlock	10487	http://www.achemblock.com/catalogsearch/result/?q=10487
AK Scientific	SYN1172	https://aksci.com/item_detail.php?cat=SYN1172
AstaTech	A12136	http://astatechinc.com/CPSResult.php?CRNO=A12136
AstaTech	F21489	http://astatechinc.com/CPSResult.php?CRNO=F21489
Axon MedChem	1401	https://www.axonmedchem.com/product/1401
Axon MedChem	2362	https://www.axonmedchem.com/product/2362
BLD Pharm	BD227929	http://www.bldpharm.com/search/Search.html?keyword=BD227929
BLD Pharm	BD227930	http://www.bldpharm.com/search/Search.html?keyword=BD227930
Cayman Chemical	13964	http://www.caymanchem.com/app/template/Product.vm/catalog/13964
Chem Scene	CS-5840	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5840
ChemShuttle	157293	https://www.chemshuttle.com/catalogsearch/result/?q=157293
ChemShuttle	187296	https://www.chemshuttle.com/catalogsearch/result/?q=187296
eMolecules	275059118	https://orderbb.emolecules.com/search/#?query=275059118
eMolecules	31239699	https://orderbb.emolecules.com/search/#?query=31239699
eMolecules	36367063	https://orderbb.emolecules.com/search/#?query=36367063
eMolecules	44466620	https://orderbb.emolecules.com/search/#?query=44466620
eMolecules	76746828	https://orderbb.emolecules.com/search/#?query=76746828
KeyOrganics	AS-16306	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16306
mcule	MCULE-1753942657	https://mcule.com/MCULE-1753942657/
mcule	MCULE-3989404808	https://mcule.com/MCULE-3989404808/
mcule	MCULE-7300552686	https://mcule.com/MCULE-7300552686/
mcule	MCULE-7503316765	https://mcule.com/MCULE-7503316765/
MedChem Express	HY-10195B	https://www.medchemexpress.com/search.html?q=HY-10195B&ft=&fa=&fp=
Molnova	M12593	https://www.molnova.com/en/serch-list.html?keywords=M12593
MolPort	MolPort-006-701-248	https://www.molport.com/shop/molecule-link/MolPort-006-701-248
MolPort	MolPort-039-062-164	https://www.molport.com/shop/molecule-link/MolPort-039-062-164
MolPort	MolPort-042-665-685	https://www.molport.com/shop/molecule-link/MolPort-042-665-685
MuseChem	I002216	https://www.musechem.com/product/I002216.html
MuseChem	I012254	https://www.musechem.com/product/I012254.html
MuseChem	M034961	https://www.musechem.com/product/M034961.html
TargetMol	T3689	https://www.targetmol.com/search?keyword=T3689
Tocris	4738	https://www.tocris.com/search.php?Type=QuickSearch&Value=4738
Toronto Research Chemicals	B689423	https://www.trc-canada.com/product-detail/?CatNum=B689423
Toronto Research Chemicals	R701525	https://www.trc-canada.com/product-detail/?CatNum=R701525

PubMed

Title	Date	PubMed
Docetaxel Facilitates Endothelial Dysfunction through Oxidative Stress via Modulation of Protein Kinase C Beta: The Protective Effects of Sotrastaurin.	2015-05	25634538
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Blockade of PKC-beta protects HUVEC from advanced glycation end products induced inflammation.	2010-12	20875828
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
Inhibition of protein kinase Cbeta does not improve endothelial function in type 2 diabetes.	2010-08	20444914
A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats.	2010-07	20079359
Selective inhibition of protein kinase C beta(2) attenuates inducible nitric oxide synthase-mediated cardiovascular abnormalities in streptozotocin-induced diabetic rats.	2009-10	19587355
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.	2009-07-17	19556521
Protein kinase C beta inhibitors: a new therapeutic target for diabetic nephropathy and vascular complications.	2008-06	18485142
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.	2007-12-18	18077363
Inhibition of PKC beta by ruboxistaurin does not enhance the acute blood pressure response to nitroglycerin.	2007-08	17443133
Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors.	2004-10-18	15380221
(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.	1996-07-05	8709095

Patents

Sample Use Guides

In Vivo Use Guide

32 mg/day

Route of Administration: Oral

In Vitro Use Guide

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 `Mon Mar 31 18:15:18 GMT 2025` Edited by `admin` on `Mon Mar 31 18:15:18 GMT 2025`
Record UNII	4TY24FTS56
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RUBOXISTAURIN METHANESULFONATE MONOHYDRATE

Preferred Name

English

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

Code System Code Type Description

PUBCHEM

6918370