SORBINIL

Investigational

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=CC=C2OCC[C@]3(NC(=O)NC3=O)C2=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 45 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 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetes mellitus 93 Sources: https://clinicaltrials.gov/ct2/show/NCT00000159	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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
eMolecules	32175121	https://orderbb.emolecules.com/search/#?query=32175121
eMolecules	745281	https://orderbb.emolecules.com/search/#?query=745281
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
mcule	MCULE-3041111850	https://mcule.com/MCULE-3041111850/
mcule	MCULE-9500731020	https://mcule.com/MCULE-9500731020/
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

PubMed

Title	Date	PubMed
Role of aldose reductase in the high glucose induced expression of fibronectin in human mesangial cells.	2010-07	19821053
Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle.	2010-05	20308528
Inhibition of aldose reductase attenuates endotoxin signals in human non-pigmented ciliary epithelial cells.	2010-05	20138035
Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis.	2009-12	19660963
Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue.	2009-11	19651811
Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein E-null mice.	2009-10-09	19729598
Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase.	2009-09	19616461
Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy.	2009-09	19602579
Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.	2009-08-06	19657391
The transforming growth factor-beta pathway is a common target of drugs that prevent experimental diabetic retinopathy.	2009-07	19401417
Aldose reductase deficiency in mice prevents azoxymethane-induced colonic preneoplastic aberrant crypt foci formation.	2009-05	19028703
Advances in pharmacological strategies for the prevention of cataract development.	2009-04-23	19384010
Cancer biomarker AKR1B10 and carbonyl metabolism.	2009-03-16	19028477
Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress.	2009-03-16	18845131
Prevention of posterior capsular opacification through aldose reductase inhibition.	2009-02	19011011
Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.	2009-02	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.	2009-01	18772236
Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives.	2008-12	18654858
Endotoxin causes pulmonary hypertension by upregulating smooth muscle endothelin type-B receptors: role of aldose reductase.	2008-08	18091567
The effect of hydrogen peroxide on sarco/endoplasmic and plasma membrane calcium ATPase gene expression in cultured human lens epithelial cells.	2008-07-07	19517033
Merging the binding sites of aldose and aldehyde reductase for detection of inhibitor selectivity-determining features.	2008-06-20	18495158
Current and future approaches in the prevention and treatment of diabetic retinopathy.	2008-06	19668733
Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers.	2008-04-28	18325492
Diabetic retinopathy: an update.	2008-04-18	18417817
Role of nitric oxide in regulating aldose reductase activation in the ischemic heart.	2008-04-04	18223294
Treatment of diabetic neuropathy and neuropathic pain: how far have we come?	2008-02	18227494
Endoplasmic reticulum stress and diabetic retinopathy.	2008	18629365
Tracing changes in protonation: a prerequisite to factorize thermodynamic data of inhibitor binding to aldose reductase.	2007-11-09	17905306
Aldose reductase inhibitors for the treatment of diabetic polyneuropathy.	2007-10-17	17943821
Aldose reductase-regulated tumor necrosis factor-alpha production is essential for high glucose-induced vascular smooth muscle cell growth.	2007-09	17584970
Evidence for a novel binding site conformer of aldose reductase in ligand-bound state.	2007-05-25	17418233
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
The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient.	2007	18224243
Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications.	2007	18200803
Inhibition of aldose reductase prevents lipopolysaccharide-induced inflammatory response in human lens epithelial cells.	2006-12	17122129
Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages.	2006-11	17174561
Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition.	2006-10-24	17030682
Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin E2 production in human colon cancer cells.	2006-10-01	17018629
Phenolic marine natural products as aldose reductase inhibitors.	2006-10	17067167
Synthesis and aldose reductase inhibitory activities of novel O-substituted hydroxyphenylacetic acid derivatives.	2006-10	17009299
A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy.	2006-10	17003340
Aldose reductase prevents aldehyde toxicity in cultured human lens epithelial cells.	2006-08	16631166
Redox activation of aldose reductase in the ischemic heart.	2006-06-02	16567803
Aldose reductase pathway inhibition improved vascular and C-fiber functions, allowing for pressure-induced vasodilation restoration during severe diabetic neuropathy.	2006-05	16644708
Estradiol attenuates mitochondrial depolarization in polyol-stressed lens epithelial cells.	2006-04-04	16617294
Aldose reductase regulates TGF-beta1-induced production of fibronectin and type IV collagen in cultured rat mesangial cells.	2006-04	16669970
Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells.	2006-04	16567509
High-resolution crystal structure of aldose reductase complexed with the novel sulfonyl-pyridazinone inhibitor exhibiting an alternative active site anchoring group.	2006-02-10	16337231
Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects.	2005-12	16306357

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

CP-45,634

Preferred Name

English

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

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