DrugBank: Rimexolone (DB00896)

targets (1) carriers (1)

Identification

Name

Rimexolone

Accession Number

DB00896 (APRD01220)

Type

small molecule

Groups

approved

Description

Rimexolone is a glucocorticoid steroid used to treat inflammation in the eye. It is marketed as a 1% eye drop solution under the trade name Vexol

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Vexol

Brand name mixtures

Not Available

Categories

Anti-inflammatory Agents
Corticosteroids

CAS number

49697-38-3

Weight

Average: 370.525
Monoisotopic: 370.250794954

Chemical Formula

C₂₄H₃₄O₃

InChI Key

InChIKey=QTTRZHGPGKRAFB-PAIWTFDUSA-N

InChI

InChI=1S/C24H34O3/c1-6-20(27)24(5)14(2)11-18-17-8-7-15-12-16(25)9-10-22(15,3)21(17)19(26)13-23(18,24)4/h9-10,12,14,17-19,21,26H,6-8,11,13H2,1-5H3/t14-,17?,18?,19+,21?,22+,23+,24-/m1/s1

Plain Text

IUPAC Name

(2R,13R,14S,15S,17S)-17-hydroxy-2,13,14,15-tetramethyl-14-propanoyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-5-one

SMILES

CCC(=O)[C@@]1(C)[C@H](C)CC2C3CCC4=CC(=O)C=C[C@]4(C)C3[C@@H](O)C[C@]12C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Carbonyl Compounds
Hydroxy Compounds
Alkanes and Alkenes
Alcohols and Polyols
Ketones

Pharmacology

Indication

For the treatment of postoperative inflammation following ocular surgery and in the treatment of anterior uveitis.

Pharmacodynamics

Rimexolone is a glucocorticoid corticosteroid for systemic use. Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They inhibit edema, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and scar formation associated with inflammation.

Mechanism of action

Rimexolone is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition of arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. By binding to the glucocorticoid receptor, this drug ultimately leads to changes in genetic transcription involving the lipocortins and prostaglandins.

Absorption

Systemically absorbed.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Undergoes extensive metabolism. Following intravenous administration of radiolabeled rimexolone in rats, more than 80% of the dose was excreted in the feces as rimexolone and metabolites. Metabolites have been shown to be either less active than rimexolone or inactive in human glucocorticoid receptor binding assays.

Route of elimination

Following IV administration of radio-labelled rimexolone to rats, greater than 80% of the dose is excreted via the feces as rimexolone and metabolites.

Half life

The serum half-life of rimexolone could not be reliably estimated due to the large number of samples below the quantitation limit of the assay (80 pg/mL). However, based on the time required to reach steady-state, the half-life appears to be short (1-2 hours).

Clearance

Not Available

Toxicity

Symptoms of overdose include retinal toxicity, glaucoma, and subcapsular cataract.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Alcon laboratories inc

Packagers

Alcon Laboratories

Dosage forms

Form	Route	Strength
Suspension	Ophthalmic

Prices

Unit description	Cost	Unit
Vexol 1% Suspension 10ml Bottle	74.08 USD	bottle
Vexol 1% Suspension 5ml Bottle	48.29 USD	bottle
Vexol 1% eye drops	7.14 USD	ml

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
water solubility	Insoluble	PhysProp
logP	4.2	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.21e-02 g/l	ALOGPS
logP	3.64	ALOGPS
logP	4.38	ChemAxon Molconvert
logS	-4.48	ALOGPS
pKa	19.86	ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	54.37	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	109.07	ChemAxon Molconvert
polarizability	43.03	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D05729
PubChem Compound	39507
PubChem Substance	46504820
ChemSpider	36120
Therapeutic Targets Database	DAP000420
PharmGKB	PA451254
Drug Product Database	2163691
RxList	http://www.rxlist.com/cgi/generic3/rimexol.htm
Drugs.com	http://www.drugs.com/cdi/rimexolone.html
Wikipedia	http://en.wikipedia.org/wiki/Rimexolone

ATC Codes

H02AB12
S01BA13

AHFS Codes

52:08.08

PDB Entries

Not Available

FDA label

show (108.2 KB)

MSDS

show (248.2 KB)

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. Glucocorticoid receptor Pharmacological action: yes Actions: agonist Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth Organism class: human UniProt ID: P04150 Gene: NR3C1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Hochhaus G, Moellmann HW: Binding affinities of rimexolone (ORG 6216), flunisolide and their putative metabolites for the glucocorticoid receptor of human synovial tissue. Agents Actions. 1990 Jun;30(3-4):377-80. Pubmed

Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out

Gene: NR3C1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Hochhaus G, Moellmann HW: Binding affinities of rimexolone (ORG 6216), flunisolide and their putative metabolites for the glucocorticoid receptor of human synovial tissue. Agents Actions. 1990 Jun;30(3-4):377-80. Pubmed

Carriers
1. Corticosteroid-binding globulin Actions: binder Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species UniProt ID: P08185 Gene: SERPINA6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Carriers

1. Corticosteroid-binding globulin

Actions: binder

Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species

UniProt ID: P08185 Link_out

Gene: SERPINA6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.