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
Thumb
Synonyms
  • Rimexolon
  • Rimexolona
External IDs
Org 6216
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VexolSuspension / drops10 mg/1mLOphthalmicAlcon, Inc.1995-09-15Not applicableUs
Vexol Ophthalmic Suspension - 1%Suspension1 %OphthalmicAlcon, Inc.1997-01-222016-06-16Canada
Categories
UNII
O7M2E4264D
CAS number
49697-38-3
Weight
Average: 370.533
Monoisotopic: 370.250794955
Chemical Formula
C24H34O3
InChI Key
QTTRZHGPGKRAFB-OOKHYKNYSA-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
IUPAC Name
(1S,2R,10S,11S,13R,14S,15S,17S)-17-hydroxy-2,13,14,15-tetramethyl-14-propanoyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-5-one
SMILES
[H][C@@]12C[C@@H](C)[C@](C)(C(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C

Pharmacology

Indication

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

Associated Conditions
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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D05729
PubChem Compound
5311412
PubChem Substance
46504820
ChemSpider
4470902
ChEBI
135566
ChEMBL
CHEMBL1200617
Therapeutic Targets Database
DAP000420
PharmGKB
PA164752251
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rimexolone
ATC Codes
H02AB12 — RimexoloneS01BA13 — Rimexolone
FDA label
Download (108 KB)
MSDS
Download (248 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentEye Dryness1
4CompletedTreatmentIntraocular Pressure1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
Packagers
  • Alcon Laboratories
Dosage forms
FormRouteStrength
Suspension / dropsOphthalmic10 mg/1mL
SuspensionOphthalmic1 %
Prices
Unit descriptionCostUnit
Vexol 1% Suspension 10ml Bottle74.08USD bottle
Vexol 1% Suspension 5ml Bottle48.29USD bottle
Vexol 1% eye drops7.14USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP4.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0121 mg/mLALOGPS
logP3.64ALOGPS
logP4.38ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)18.76ChemAxon
pKa (Strongest Basic)-0.21ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity109.07 m3·mol-1ChemAxon
Polarizability42.91 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9796
Caco-2 permeable+0.7879
P-glycoprotein substrateSubstrate0.7261
P-glycoprotein inhibitor IInhibitor0.616
P-glycoprotein inhibitor IIInhibitor0.5126
Renal organic cation transporterNon-inhibitor0.8022
CYP450 2C9 substrateNon-substrate0.8142
CYP450 2D6 substrateNon-substrate0.9195
CYP450 3A4 substrateSubstrate0.7631
CYP450 1A2 substrateNon-inhibitor0.9521
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.6544
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7217
Ames testNon AMES toxic0.9396
CarcinogenicityNon-carcinogens0.9243
BiodegradationNot ready biodegradable0.9906
Rat acute toxicity2.1317 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8573
hERG inhibition (predictor II)Non-inhibitor0.7387
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-2910000000-2f40fe36282161d91be9

Taxonomy

Description
This compound belongs to the class of organic compounds known as 20-oxosteroids. These are steroid derivatives carrying a C=O group at the 20-position of the steroid skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Oxosteroids
Direct Parent
20-oxosteroids
Alternative Parents
Androgens and derivatives / 3-oxo delta-1,4-steroids / 11-beta-hydroxysteroids / Delta-1,4-steroids / Secondary alcohols / Cyclic ketones / Cyclic alcohols and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
20-oxosteroid / Androgen-skeleton / Androstane-skeleton / 3-oxo-delta-1,4-steroid / 3-oxosteroid / Hydroxysteroid / 11-beta-hydroxysteroid / 11-hydroxysteroid / Delta-1,4-steroid / Cyclic alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. 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:2386110]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Shukla SJ, Sakamuru S, Huang R, Moeller TA, Shinn P, Vanleer D, Auld DS, Austin CP, Xia M: Identification of clinically used drugs that activate pregnane X receptors. Drug Metab Dispos. 2011 Jan;39(1):151-9. doi: 10.1124/dmd.110.035105. Epub 2010 Oct 21. [PubMed:20966043]
  2. NCI/NIH [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 05, 2018 17:48