Loteprednol etabonate
Explore a selection of our essential drug information below, or:
Identification
- Summary
Loteprednol etabonate is a corticosteroid used to treat allergic conjunctivitis as well as inflammation and pain after ocular surgery.
- Brand Names
- Alrex, Eysuvis, Inveltys, Lotemax, Zylet
- Generic Name
- Loteprednol etabonate
- DrugBank Accession Number
- DB14596
- Background
Loteprednol Etabonate (LE) is a topical corticoid anti-inflammatory. It is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitides. As a nasal spray, it can be used for the treatment and management of seasonal allergic rhinitis.
Most prescription LE products, however, tend to be indicated for the treatment of post-operative inflammation and pain following ocular surgery Label. A number of such new formulations that have been approved include Kala Pharmaceutical's Inveltys - the first twice-daily (BID) ocular corticosteroid approved for this indication, designed specifically to enhance patient compliance and simplified dosing compared to all other similar ocular steroids that are dosed four times daily 6.
Moreover, LE was purposefully engineered to be a 'soft drug', one that is designed to be active locally at the site of administration and then rapidly metabolized to inactive components after eliciting its actions at the desired location, thereby subsequently minimizing the chance for adverse effects 4.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 466.96
Monoisotopic: 466.175831 - Chemical Formula
- C24H31ClO7
- Synonyms
- Loteprednol etabonate
- External IDs
- CDDD 5604
- CDDD-5604
- HGP 1
- HGP-1
- KPI-121
- P 5604
- P-5604
Pharmacology
- Indication
A number of prescription loteprednol etabonate ophthalmic products are specifically indicated for the treatment of post-operative inflammation and pain following ocular surgery Label.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Dry eye syndrome (des) •••••••••••• •••••••••• Treatment of Eye pain •••••••••••• Treatment of Eye inflammation •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Loteprednol etabonate (LE) belongs to a unique class of corticosteroids with potent anti-inflammatory effects designed to be active at the site of action 1,5. Animal studies have shown that LE has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone 5. This particular class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body 5. Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity 5. Specifically, LE is an ester derivative of one of these analogs, cortienic acid etabonate 5. In particular, LE possesses a metabolically labile 17 beta-chloromethyl ester function which was designed in order to be hydrolyzed to an inactive carboxylic acid moiety 1. This inactive metabolite is more hydrophilic and is thus readily eliminated from the body 1. LE also exhibits good ocular permeation properties and good skin permeation properties 1.
- Mechanism of action
Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing Label,5,1. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly associated with inflammation Label,1. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established Label,5,1. Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms Label,1. In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins 8. 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 8. Arachidonic acid is released from membrane phospholipids by phospholipase A2 8.
The use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery 1.
Target Actions Organism ASteroid hormone receptor ERR1 modulatorHumans ASteroid hormone receptor ERR2 modulatorHumans AEstrogen-related receptor gamma modulatorHumans AGlucocorticoid receptor agonistHumans - Absorption
Loteprednol etabonate (LE) demonstrates good ocular permeation properties as it is lipid soluble, allowing the agent to penetrate into cells with relative ease Label,1.
Results from the ocular administration of loteprednol in normal, healthy volunteers have shown that there are low or undetectable concentrations of either unchanged material or its metabolite 5. Following twice-daily unilateral topical ocular dosing of LE for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all time points Label. These finds suggest that limited, if any, systemic absorption of LE occurs 5.
- Volume of distribution
The only data available regarding the volume of distribution of loteprednol etabonate (LE) is the volume of distribution the agent demonstrated when administered to dogs - a value of 3.7 L/kg 3. It has been shown, however, that the topical ocular administration of LE distributes preferentially into the cellular components of blood 8.
- Protein binding
Strong protein binding of approximately 98% for loteprednol etabonate facilitates little pharmacodynamic action and/or adverse effects on the part of the agent in the systemic circulation 2.
- Metabolism
Loteprednol etabonate (LE) is readily and extensively metabolized to two inactive metabolites, PJ-90 (Δ1-cortienic acid) and PJ-91 (Δ1-cortienic acid etabonate) Label,8. Metabolism occurs locally in ocular tissues, and to the extent that loteprednol etabonate reaches the systemic circulation, likely the liver and other tissues into which it distributes 8.
In particular, studies have demonstrated that LE (chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-3-oxoandrosta-1,4-diene) is rapidly hydrolyzed at the location of its 17beta-chloromethyl ester function by paraoxonase 1 in human plasma at the site of administration at the level of the affected eye tissue to the 17beta-carboxylate PJ-91 metabolite and PJ-90 metabolite 2,4. Both metabolites are considered inactive Label,4,4.
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- Route of elimination
Following systemic administration to rats, loteprednol etabonate is eliminated primarily via the biliary/faecal route, with most of the dose eliminated in the form of the metabolite, PJ-90 8.
- Half-life
The terminal half-life of loteprednol etabonate as determined when administered intravenously at a dose of 5 mg/kg in the dog animal model is 2.8 hours 3.
- Clearance
Loteprednol etabonate was slowly hydrolyzed in liver at clearance rates of 0.21 +/- 0.04 and 2.41 +/- 0.13 ml/h/kg in the liver and plasma, respectively 2.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The most common adverse drug reactions reported during clinical trials for the medication were eye pain and posterior capsular opacification, both of which may also be the consequence of the very surgical procedures performed on the eye(s) Label.
The agent is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug Label.
The medication is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child to the agent Label.
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay Label.
Overdose is not expected to be likely to occur after ocular administration 8.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Eysuvis / Loteflam (Cipla Pharmaceuticals Limited)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alrex Suspension / drops 2 mg/1mL Ophthalmic Bausch & Lomb Incorporated 1998-03-09 Not applicable US Alrex Suspension / drops 2 mg/1mL Ophthalmic Stat Rx USA 1998-03-09 Not applicable US Alrex Suspension 0.2 % w/v Ophthalmic Bausch & Lomb Incorporated 2009-06-24 Not applicable Canada Alrex Suspension / drops 2 mg/1mL Ophthalmic Physicians Total Care, Inc. 2002-10-17 Not applicable US Eysuvis Suspension / drops 2.5 mg/1mL Ophthalmic ALCON LABORATORIES, INC. 2020-11-18 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Loteprednol Etabonate Gel 5 mg/1g Ophthalmic Armas Pharmaceuticals Inc. 2023-10-25 Not applicable US Loteprednol Etabonate Gel 5 mg/1g Ophthalmic Bausch & Lomb Incorporated 2023-06-30 Not applicable US Loteprednol Etabonate Gel 5 mg/1g Ophthalmic Bausch & Lomb Incorporated 2021-02-17 Not applicable US Loteprednol Etabonate Suspension / drops 5 mg/1mL Ophthalmic Northstar RxLLC 2024-09-01 Not applicable US Loteprednol Etabonate Suspension / drops 5 mg/1mL Ophthalmic Oceanside Pharmaceuticals 2019-07-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image LOTEBRA % 0.5+ % 0.3 GÖZ DAMLASI, SÜSPANSİYON, 5 ML Loteprednol etabonate (0.5 %) + Tobramycin (0.3 %) Suspension / drops Ophthalmic ABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş. 2014-05-08 Not applicable Turkey LOTEMICIN® Loteprednol etabonate (5 mg) + Tobramycin (3 mg) Suspension Conjunctival; Ophthalmic LABORATORIOS POEN S.A.U. 2008-04-03 Not applicable Colombia LOTEMICIN® Loteprednol etabonate (5 mg) + Tobramycin (3 mg) Suspension Ophthalmic QUIBI S.A. EN REESTRUCTURACION 2022-09-30 Not applicable Colombia TOBRALOT 5 MG+3 MG/ML GÖZ DAMLASI, SÜSPANSİYON, 1 ADET Loteprednol etabonate (5 mg/mL) + Tobramycin (3 mg/ml) Suspension / drops Ophthalmic VEM İLAÇ SAN. VE TİC. A.Ş. 2019-11-30 Not applicable Turkey Zylet Loteprednol etabonate (5 mg/1mL) + Tobramycin (3 mg/1mL) Suspension / drops Ophthalmic Bausch & Lomb Incorporated 2004-12-14 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Steroid esters
- Direct Parent
- Steroid esters
- Alternative Parents
- Androgens and derivatives / 3-oxo delta-1,4-steroids / 11-beta-hydroxysteroids / Delta-1,4-steroids / Carbonic acid diesters / Secondary alcohols / Cyclic ketones / Cyclic alcohols and derivatives / Carboxylic acid esters / Monocarboxylic acids and derivatives show 4 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / Alcohol / Aliphatic homopolycyclic compound / Alkyl chloride / Alkyl halide / Androgen-skeleton / Androstane-skeleton show 20 more
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- organochlorine compound, 11beta-hydroxy steroid, steroid ester, etabonate ester, 3-oxo-Delta(1),Delta(4)-steroid, steroid acid ester (CHEBI:31784)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- YEH1EZ96K6
- CAS number
- 82034-46-6
- InChI Key
- DMKSVUSAATWOCU-HROMYWEYSA-N
- InChI
- InChI=1S/C24H31ClO7/c1-4-30-21(29)32-24(20(28)31-13-25)10-8-17-16-6-5-14-11-15(26)7-9-22(14,2)19(16)18(27)12-23(17,24)3/h7,9,11,16-19,27H,4-6,8,10,12-13H2,1-3H3/t16-,17-,18-,19+,22-,23-,24-/m0/s1
- IUPAC Name
- chloromethyl (1R,3aS,3bS,9aR,9bS,10S,11aS)-1-[(ethoxycarbonyl)oxy]-10-hydroxy-9a,11a-dimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1-carboxylate
- SMILES
- [H][C@@]12CC[C@](OC(=O)OCC)(C(=O)OCCl)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
References
- General References
- Pavesio CE, Decory HH: Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9. doi: 10.1136/bjo.2007.132621. Epub 2008 Feb 1. [Article]
- Samir A, Bodor N, Imai T: Identification of esterase involved in the metabolism of two corticosteroid soft drugs. Biochem Pharmacol. 2017 Mar 1;127:82-89. doi: 10.1016/j.bcp.2016.12.010. Epub 2016 Dec 22. [Article]
- Hochhaus G, Chen LS, Ratka A, Druzgala P, Howes J, Bodor N, Derendorf H: Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs. J Pharm Sci. 1992 Dec;81(12):1210-5. [Article]
- Druzgala P, Wu WM, Bodor N: Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991 Oct;10(10):933-7. [Article]
- Electronic Medicines Compendium: Loteprednol etabonate Monograph [Link]
- Inveltys FDA Approval Press Release [Link]
- FDA Approved Drug Products: Eysuvis (loteprednol etabonate) ophthalmic suspension [Link]
- Australian Register of Therapeutic Goods: Loteprednol etabonate Product Information [File]
- External Links
- Human Metabolome Database
- HMDB0015011
- KEGG Drug
- D01689
- PubChem Compound
- 9865442
- PubChem Substance
- 46504713
- ChemSpider
- 392049
- BindingDB
- 50248301
- ChEBI
- 31784
- ChEMBL
- CHEMBL1200865
- ZINC
- ZINC000003920673
- Therapeutic Targets Database
- DAP001045
- PharmGKB
- PA164764569
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Loteprednol
- FDA label
- Download (153 KB)
- MSDS
- Download (22 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Inflammation / Pseudophakia 1 somestatus stop reason just information to hide Not Available Completed Not Available Ocular Hypertension 1 somestatus stop reason just information to hide Not Available Completed Diagnostic Sjögren's Syndrome (SS) 1 somestatus stop reason just information to hide Not Available Completed Prevention Dry Eyes 1 somestatus stop reason just information to hide Not Available Completed Treatment Diabetic Macular Edema (DME) / Retinal Vein Occlusion 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Bausch and lomb inc
- Pharmos corp
- Packagers
- Alchymars SPA
- Bausch & Lomb Inc.
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Suspension Conjunctival 0.20 %w/v Suspension Ophthalmic 0.2 % w/v Suspension / drops Ophthalmic 2 mg/1mL Suspension Ophthalmic 5 mg Solution / drops Ophthalmic 0.5 % Suspension / drops Ophthalmic 2.5 mg/1mL Suspension Topical 10 mg/1mL Suspension Ophthalmic 0.5 % Gel Ophthalmic 5 mg/1g Ointment Ophthalmic 5 mg/1g Solution / drops Intraocular Suspension Ophthalmic 0.5 % w/v Suspension / drops Ophthalmic 5 mg/1mL Suspension / drops Ophthalmic 0.5 % Suspension / drops Ophthalmic 5 mg/ml Gel Ophthalmic 0.5 % w/w Ointment Ophthalmic 0.5 % w/w Gel Ophthalmic 3.8 mg/1g Suspension Ophthalmic Solution Ophthalmic 5 mg/ml Suspension Conjunctival; Ophthalmic Suspension Conjunctival; Ophthalmic 0.002 g Suspension Conjunctival; Ophthalmic 5 mg Ointment Ophthalmic; Topical 500 mg Suspension Conjunctival; Ophthalmic 500000 mg Suspension Ophthalmic 2 mg Suspension / drops Ophthalmic Suspension Ophthalmic - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5540930 No 1996-07-30 2013-10-25 US US4996335 No 1991-02-26 2012-03-09 US CA2174550 No 2002-10-01 2014-10-21 Canada US5800807 No 1998-09-01 2017-01-29 US US9056057 No 2015-06-16 2033-05-03 US US9532955 No 2017-01-03 2033-05-03 US US9827191 No 2017-11-28 2033-05-03 US US10058511 No 2018-08-28 2033-05-03 US US9737491 No 2017-08-22 2033-05-03 US US9393213 No 2016-07-19 2033-05-03 US US10596107 No 2020-03-24 2036-12-23 US US10646437 No 2020-05-12 2033-05-03 US US10688045 No 2020-06-23 2033-05-03 US US10857096 No 2020-12-08 2033-05-03 US US10864219 No 2020-12-15 2033-05-03 US US10646436 No 2020-05-12 2033-05-03 US US10945948 No 2021-03-16 2033-05-03 US US10940108 No 2021-03-09 2033-05-03 US US10993908 No 2021-05-04 2033-05-03 US US11219596 No 2013-05-03 2033-05-03 US US11219597 No 2013-05-03 2033-05-03 US US11534395 No 2016-01-26 2036-01-26 US US11596599 No 2013-05-03 2033-05-03 US US11642317 No 2013-05-03 2033-05-03 US US11872318 No 2013-05-03 2033-05-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 220-224 °C Not Available water solubility 5 mg/mL Not Available logP 3.4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00693 mg/mL ALOGPS logP 3.08 ALOGPS logP 3.94 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 14.88 Chemaxon pKa (Strongest Basic) -2.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 99.13 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 118.17 m3·mol-1 Chemaxon Polarizability 48.43 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9884 Blood Brain Barrier + 0.9294 Caco-2 permeable + 0.5426 P-glycoprotein substrate Substrate 0.7489 P-glycoprotein inhibitor I Non-inhibitor 0.6379 P-glycoprotein inhibitor II Non-inhibitor 0.6419 Renal organic cation transporter Non-inhibitor 0.7633 CYP450 2C9 substrate Non-substrate 0.862 CYP450 2D6 substrate Non-substrate 0.914 CYP450 3A4 substrate Substrate 0.794 CYP450 1A2 substrate Non-inhibitor 0.8987 CYP450 2C9 inhibitor Non-inhibitor 0.8866 CYP450 2D6 inhibitor Non-inhibitor 0.872 CYP450 2C19 inhibitor Non-inhibitor 0.9233 CYP450 3A4 inhibitor Non-inhibitor 0.5687 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8468 Ames test Non AMES toxic 0.8574 Carcinogenicity Non-carcinogens 0.9436 Biodegradation Not ready biodegradable 0.9614 Rat acute toxicity 2.2305 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9647 hERG inhibition (predictor II) Non-inhibitor 0.5773
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 204.04366 predictedDeepCCS 1.0 (2019) [M+H]+ 205.97337 predictedDeepCCS 1.0 (2019) [M+Na]+ 213.15541 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle
- Specific Function
- DNA-binding transcription factor activity
- Gene Name
- ESRRA
- Uniprot ID
- P11474
- Uniprot Name
- Steroid hormone receptor ERR1
- Molecular Weight
- 45509.11 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)
- Specific Function
- cis-regulatory region sequence-specific DNA binding
- Gene Name
- ESRRB
- Uniprot ID
- O95718
- Uniprot Name
- Steroid hormone receptor ERR2
- Molecular Weight
- 48053.14 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle
- Specific Function
- AF-2 domain binding
- Gene Name
- ESRRG
- Uniprot ID
- P62508
- Uniprot Name
- Estrogen-related receptor gamma
- Molecular Weight
- 51305.485 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). 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 modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). 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 (By similarity)
- Specific Function
- core promoter sequence-specific DNA binding
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
- Druzgala P, Hochhaus G, Bodor N: Soft drugs--10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol. 1991 Feb;38(2):149-54. [Article]
- Bodor N, Buchwald P: Corticosteroid design for the treatment of asthma: structural insights and the therapeutic potential of soft corticosteroids. Curr Pharm Des. 2006;12(25):3241-60. [Article]
- Szelenyi I, Hochhaus G, Heer S, Kusters S, Marx D, Poppe H, Engel J: Loteprednol etabonate: a soft steroid for the treatment of allergic diseases of the airways. Drugs Today (Barc). 2000 May;36(5):313-20. [Article]
- Samudre SS, Lattanzio FA Jr, Williams PB, Sheppard JD Jr: Comparison of topical steroids for acute anterior uveitis. J Ocul Pharmacol Ther. 2004 Dec;20(6):533-47. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation
- Specific Function
- acyl-L-homoserine-lactone lactonohydrolase activity
- Gene Name
- PON1
- Uniprot ID
- P27169
- Uniprot Name
- Serum paraoxonase/arylesterase 1
- Molecular Weight
- 39730.99 Da
References
- Samir A, Bodor N, Imai T: Identification of esterase involved in the metabolism of two corticosteroid soft drugs. Biochem Pharmacol. 2017 Mar 1;127:82-89. doi: 10.1016/j.bcp.2016.12.010. Epub 2016 Dec 22. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 08:50