SORBINIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H9FN2O3
Molecular Weight	236.1992
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC2=C(OCC[C@]23NC(=O)NC3=O)C=C1

InChI

InChIKey=LXANPKRCLVQAOG-NSHDSACASA-N

InChI=1S/C11H9FN2O3/c12-6-1-2-8-7(5-6)11(3-4-17-8)9(15)13-10(16)14-11/h1-2,5H,3-4H2,(H2,13,14,15,16)/t11-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT00000159 | https://www.ncbi.nlm.nih.gov/pubmed/2012352

Sorbinil (also known as CP-45,634), an aldose reductase inhibitor that has been in phase III clinical trials in preventing the development of diabetic retinopathy and neuropathy in persons with insulin-dependent diabetes. However, this research has been discontinued. It is also known, that sorbinil is oxidatively metabolized to a potentially toxic intermediate.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aldose reductase 44 Target ID: P15121 Gene ID: 231.0 Gene Symbol: AKR1B1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/122297	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetes mellitus 91 Sources: https://clinicaltrials.gov/ct2/show/NCT00000159	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6.25 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.36 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
528 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
547 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
58.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
76.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3107606	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		SORBINIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	ACM69684839	http://www.alfa-chemistry.com/search.aspx?q=ACM69684839
Apollo Scientific	PC9879	http://www.apolloscientific.co.uk/chemical_results.php?qstext=PC9879&product_group=%25&search_fieldname=header_search
BOC Sciences	68367-52-2	http://www.bocsci.com/description.asp?cas=68367-52-2
Fluoropharm	OF23470	http://www.fluoropharm.com/product/OF23470.html
Indofine	26-887	https://indofinechemical.com/details.aspx?Sku=26-887
KeyOrganics	FS-1063	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=FS-1063
MolPort	MolPort-000-155-556	https://www.molport.com/shop/molecule-link/MolPort-000-155-556
MolPort	MolPort-000-883-094	https://www.molport.com/shop/molecule-link/MolPort-000-883-094
MuseChem	M017861	https://www.musechem.com/product/M017861.html
Oakwood	3847	http://www.oakwoodchemical.com/ProductsList.aspx?txtSearch=003847
SynQuest	15485	http://www.synquestlabs.com/search-result.html?q=15485
SynQuest	4H48-3-64	http://www.synquestlabs.com/search-result.html?q=4H48-3-64
Tetrahedron	TS56760	http://www.thsci.com/search.do?q=TS56760
Tetrahedron	TS56761	http://www.thsci.com/search.do?q=TS56761
TimTec	SBB098563	http://www.echemstore.com/catalogsearch/result/?q=SBB098563
TimTec	ST45399422	http://www.echemstore.com/catalogsearch/result/?q=ST45399422
eMolecules	32175121	https://orderbb.emolecules.com/search/#?query=32175121
eMolecules	745281	https://orderbb.emolecules.com/search/#?query=745281
mcule	MCULE-3041111850	https://mcule.com/MCULE-3041111850/
mcule	MCULE-9500731020	https://mcule.com/MCULE-9500731020/

PubMed

Title	Date	PubMed
Glucose-mediated induction of TGF-beta 1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent.	2003 Apr	12631356
Incorporation of clustering effects for the Wilcoxon rank sum test: a large-sample approach.	2003 Dec	14969489
A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat.	2003 Feb	12540628
Metabolism of lipid derived aldehyde, 4-hydroxynonenal in human lens epithelial cells and rat lens.	2003 Jun	12766072
Synthesis, activity, and molecular modeling studies of novel human aldose reductase inhibitors based on a marine natural product.	2003 Nov 20	14613323
Rapid stimulation of free glucuronate formation by non-glucuronidable xenobiotics in isolated rat hepatocytes.	2003 Sep 19	12865420
Glycogenolysis is directed towards ascorbate synthesis by glutathione conjugation.	2004 Apr 23	15047160
Inhibition of aldose reductase attenuates TNF-alpha-induced expression of adhesion molecules in endothelial cells.	2004 Aug	15284221
Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004?	2004 Dec	15539002
Aldose reductase-catalyzed reduction of aldehyde phospholipids.	2004 Dec 17	15465833
Aldose reductase regulates TNF-alpha-induced cell signaling and apoptosis in vascular endothelial cells.	2004 Jul 16	15251463
[Effects of Shendan Jianyi Capsule on aldose reductase activity of kidney in diabetic rats].	2004 Mar	15339475
Activation of nuclear factor-kappaB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase.	2004 Nov	15504972
Multiple imputation to estimate the association between eyes in disease progression with interval-censored data.	2004 Nov 15	15493063
Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy.	2004 Sep	15331552
Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity.	2005 Aug 25	16107153
Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects.	2005 Dec	16306357
Spirohydantoin derivatives of thiopyrano[2,3-b]pyridin-4(4H)-one as potent in vitro and in vivo aldose reductase inhibitors.	2005 Jan 17	15598571
[Effects of aldose reductase transfection on the proliferation of rat mesangial cells in vitro].	2005 Jul	16251047
[Effects of aldose reductase on the transforming growth factor-beta1-induced expression of fibronectin and collagen IV: experiment with cultured rat mesangial cells].	2005 Jul 13	16253186
[Potential pharmacological treatments for diabetic retinopathy].	2005 Jun	15999714
[Effects of aldose reductase on the expression of fibronectin and collagen IV in cultured rat renal mesangial cells].	2005 Mar	15938830
Ciglitazone-induced lenticular opacities in rats: in vivo and whole lens explant culture evaluation.	2005 Mar	15523002
Factorizing selectivity determinants of inhibitor binding toward aldose and aldehyde reductases: structural and thermodynamic properties of the aldose reductase mutant Leu300Pro-fidarestat complex.	2005 Sep 8	16134934
Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells.	2006 Apr	16567509
Estradiol attenuates mitochondrial depolarization in polyol-stressed lens epithelial cells.	2006 Apr 4	16617294
Aldose reductase prevents aldehyde toxicity in cultured human lens epithelial cells.	2006 Aug	16631166
Inhibition of aldose reductase prevents lipopolysaccharide-induced inflammatory response in human lens epithelial cells.	2006 Dec	17122129
Preservation of pressure-induced cutaneous vasodilation by limiting oxidative stress in short-term diabetic mice.	2006 Jan	16266692
Synthesis and aldose reductase inhibitory activities of novel O-substituted hydroxyphenylacetic acid derivatives.	2006 Oct	17009299
Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin E2 production in human colon cancer cells.	2006 Oct 1	17018629
Cellular signaling and potential new treatment targets in diabetic retinopathy.	2007	18288248
Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy.	2007	18274606
Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications.	2007	18200803
Evidence for a novel binding site conformer of aldose reductase in ligand-bound state.	2007 May 25	17418233
Tracing changes in protonation: a prerequisite to factorize thermodynamic data of inhibitor binding to aldose reductase.	2007 Nov 9	17905306
Aldose reductase inhibitors for the treatment of diabetic polyneuropathy.	2007 Oct 17	17943821
Role of nitric oxide in regulating aldose reductase activation in the ischemic heart.	2008 Apr 4	18223294
Endotoxin causes pulmonary hypertension by upregulating smooth muscle endothelin type-B receptors: role of aldose reductase.	2008 Aug	18091567
Current and future approaches in the prevention and treatment of diabetic retinopathy.	2008 Jun	19668733
Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.	2009 Aug 6	19657391
Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis.	2009 Dec	19660963
Prevention of posterior capsular opacification through aldose reductase inhibition.	2009 Feb	19011011
Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.	2009 Feb	19010934
Aldose reductase regulates high glucose-induced ectodomain shedding of tumor necrosis factor (TNF)-alpha via protein kinase C-delta and TNF-alpha converting enzyme in vascular smooth muscle cells.	2009 Jan	18772236
Cancer biomarker AKR1B10 and carbonyl metabolism.	2009 Mar 16	19028477
Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress.	2009 Mar 16	18845131
Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy.	2009 Sep	19602579
Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle.	2010 May	20308528
Inhibition of aldose reductase attenuates endotoxin signals in human non-pigmented ciliary epithelial cells.	2010 May	20138035

Patents

Sample Use Guides

In Vivo Use Guide

250-mg tablet daily

Route of Administration: Oral

In Vitro Use Guide

Microsome-generated metabolites of sorbinil (50 microM) were toxic to normal peripheral blood lymphocytes (7.9% +/- 0.3% dead cells [mean +/- SE]). Toxicity was increased in the presence of an epoxide hydrolase inhibitor and abolished by an inhibitor of cytochrome P-450. In contrast to cells from healthy controls and diabetics who tolerated sorbinil, cells from the six patients who had sorbinil reactions showed significantly increased toxicity from metabolites of sorbinil and phenytoin. It was concluded that sorbinil is oxidatively metabolized to a potentially toxic intermediate.

Name

Type

Language

SORBINIL

Official Name

English

NSC-355082

Code

English

(S)-6-FLUOROSPIRO(CHROMAN-4,4'-IMIDAZOLIDINE)-2',5'-DIONE

Systematic Name

English

Sorbinil [WHO-DD]

Common Name

English

SORBINIL [MART.]

Common Name

English

SORBINIL [USAN]

Common Name

English

CP-45,634

Code

English

SPIRO(4H-1-BENZOPYRAN-4,4'-IMIDAZOLIDINE)-2',5'-DIONE, 6-FLUORO-2,3-DIHYDRO-, (S)-

Systematic Name

English

SORBINIL [MI]

Common Name

English

sorbinil [INN]

Common Name

English

CP-45634

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C72880