Identification

Name
Medrysone
Accession Number
DB00253  (APRD01091)
Type
Small Molecule
Groups
Approved
Description

Medrysone is a corticosteroid used in ophthalmology. [Wikipedia]

Structure
Thumb
Synonyms
  • 11beta-Hydroxy-6alpha-methylpregn-4-ene-3,20-dione
External IDs
NSC-63278 / U-8471
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HmsSolution / drops1 %OphthalmicAllergan1969-12-312011-08-04Canada
HmsSuspension10 mg/1mLOphthalmicAllergan2006-02-28Not applicableUs
International/Other Brands
HMS
Categories
UNII
D2UFC189XF
CAS number
2668-66-8
Weight
Average: 344.4877
Monoisotopic: 344.23514489
Chemical Formula
C22H32O3
InChI Key
GZENKSODFLBBHQ-ILSZZQPISA-N
InChI
InChI=1S/C22H32O3/c1-12-9-15-17-6-5-16(13(2)23)22(17,4)11-19(25)20(15)21(3)8-7-14(24)10-18(12)21/h10,12,15-17,19-20,25H,5-9,11H2,1-4H3/t12-,15-,16+,17-,19-,20+,21-,22+/m0/s1
IUPAC Name
(1S,2R,8S,10S,11S,14S,15S,17S)-14-acetyl-17-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)CC[C@]12C

Pharmacology

Indication

For the treatment of allergic conjunctivitis, vernal conjunctivitis, episcleritis, and epinephrine sensitivity.

Pharmacodynamics

Medrysone is a topical anti-inflammatory corticoidsteroids for ophthalmic use. In patients with increased intraocular pressure and in those susceptible to a rise in intraocular pressure, there is less effect on pressure with medrysone than with dexamethasone or betamethasone. Corticoidsteroids inhibit the edema, fibrin deposition, capillary dilation, and phagocytic migration of the acute inflammatory response, as well as capillary proliferation, deposition of collagen, and scar formation.

Mechanism of action

There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Initially, the drug binds to the glucocorticoid receptor in the cytosol. This migrates to the nucleus and binds to genetic elements which cause activation and repression of the involved genes in the inflammatory pathway.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
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
Human Metabolome Database
HMDB0014398
KEGG Drug
D02289
KEGG Compound
C14643
PubChem Compound
247839
PubChem Substance
46506584
ChemSpider
216968
ChEBI
34829
ChEMBL
CHEMBL1201173
Therapeutic Targets Database
DAP001048
PharmGKB
PA450346
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Medrysone
ATC Codes
S01BA08 — Medrysone
FDA label
Download (149 KB)
MSDS
Download (48.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Allergan pharmaceutical
Packagers
Not Available
Dosage forms
FormRouteStrength
Solution / dropsOphthalmic1 %
SuspensionOphthalmic10 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156.5 °CPhysProp
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0337 mg/mLALOGPS
logP3.06ALOGPS
logP3.13ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)19.14ChemAxon
pKa (Strongest Basic)-0.26ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity98.85 m3·mol-1ChemAxon
Polarizability39.92 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+0.9705
Caco-2 permeable+0.8125
P-glycoprotein substrateSubstrate0.6825
P-glycoprotein inhibitor IInhibitor0.6076
P-glycoprotein inhibitor IINon-inhibitor0.7298
Renal organic cation transporterNon-inhibitor0.7757
CYP450 2C9 substrateNon-substrate0.7961
CYP450 2D6 substrateNon-substrate0.9127
CYP450 3A4 substrateSubstrate0.7688
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.869
CYP450 2D6 inhibitorNon-inhibitor0.9491
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9052
Ames testNon AMES toxic0.9525
CarcinogenicityNon-carcinogens0.9338
BiodegradationNot ready biodegradable0.9822
Rat acute toxicity2.3015 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8934
hERG inhibition (predictor II)Non-inhibitor0.7724
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0329000000-a39ea3d5131dd74530f9
MS/MS Spectrum - , positiveLC-MS/MSsplash10-053j-3920000000-e4a574efed2d534b983c

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxo delta-4-steroids / 11-beta-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Secondary alcohols / Cyclic alcohols and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Hydroxysteroid / Oxosteroid / Delta-4-steroid / Cyclohexenone
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
corticosteroid hormone (CHEBI:34829)

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. Southren AL, Dominguez MO, Gordon GG, Wenk EJ, Hernandez MR, Dunn MW, Weinstein BI: Nuclear translocation of the cytoplasmic glucocorticoid receptor in the iris-ciliary body and adjacent corneoscleral tissue of the rabbit following topical administration of various glucocorticoids. A rapid screening method for glucocorticoid activity. Invest Ophthalmol Vis Sci. 1983 Feb;24(2):147-52. [PubMed:6336597]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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. NCI/NIH [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:40