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Identification
- Summary
Adapalene is a third-generation topical retinoid with anti-comedogenic, comedolytic, and anti-inflammatory properties used to treat acne vulgaris in adolescents and adults.
- Brand Names
- Cabtreo, Differin, Epiduo, Panoxyl, Tactupump
- Generic Name
- Adapalene
- DrugBank Accession Number
- DB00210
- Background
Acne vulgaris is a multifactorial disorder of the pilosebaceous unit involving increased sebum production, inflammation, and hyperproliferation/hyperkeratinization of the follicular infundibulum. It is also associated with Cutibacterium acnes (also known as Propionibacterium acnes). Adapalene is a third-generation topical retinoid used for the treatment of acne vulgaris.4 Adapalene has similar efficacy but a superior safety profile compared to tretinoin.5 Tazarotene is more efficacious than adapalene but is designated as pregnancy category X and hence is contraindicated in pregnant women.4 Adapalene can also be combined with benzoyl peroxide (BPO), which possesses bactericidal properties6, and either adapalene alone, or adapalene BPO combination products, are commonly used to treat mild-to-severe acne.4
Differin®, produced by Galderma Labs, was first granted FDA approval on May 31st, 1996, as a 0.1% adapalene topical solution. Differin was later made available as 0.1% gel, cream, or lotion, or 0.3% gel products. On December 8th, 2008, Galderma Labs gained FDA approval for Epiduo®, a 0.1% adapalene, 2.5% BPO combination gel.8
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Adapalene (DB00210)
- Weight
- Average: 412.5201
Monoisotopic: 412.203844762 - Chemical Formula
- C28H28O3
- Synonyms
- 6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid
- Adapalene
- Adapalène
- Adapaleno
- Adapalenum
- External IDs
- CD 271
- CD-271
Pharmacology
- Indication
Adapalene is indicated for the topical treatment of acne vulgaris in patients aged 12 and over.8 It is also indicated for acne vulgaris in combination with benzoyl peroxide11 and in a triple combination therapy with benzoyl peroxide and clindamycin.13
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 Used in combination to treat Acne vulgaris Combination Product in combination with: Benzoyl peroxide (DB09096), Clindamycin (DB01190) •••••••••••• ••• Used in combination to treat Acne vulgaris Combination Product in combination with: Benzoyl peroxide (DB09096) •••••••••••• ••• Treatment of Acne vulgaris •••••••••••• ••• Treatment of Acne vulgaris ••• ••• •••••• •••• •••••• - 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
Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response.2 Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.8
- Mechanism of action
Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity.1 Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation7, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation.3 These effects primarily account for adapalene's comedolytic and anticomedogenic properties.
In addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes Cutibacterium acnes (formerly Propionibacterium acnes), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms.2
When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.2
Target Actions Organism ARetinoic acid receptor beta agonistHumans ARetinoic acid receptor gamma agonistHumans ARetinoic acid receptor RXR-beta agonistHumans ARetinoic acid receptor RXR-gamma agonistHumans ARetinoic acid receptor RXR-alpha agonistHumans ATranscription factor Jun antagonistHumans AToll-like receptor 2 antagonistHumans URetinoic acid receptor alpha Not Available Humans UAspartate aminotransferase, cytoplasmic inhibitorHumans - Absorption
Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm2 of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean Cmax of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng*h/ml on day 10.8
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug.9
- Route of elimination
Adapalene is primarily excreted by the biliary route at about 30 ng/g of the topically applied amount. Approximately 75% of the drug remains unchanged.1
- Half-life
In one clinical study, after ten days of treatment with 2g of 0.3% cream or gel, the terminal half-life was between 7 and 51 hours, with a mean of 17.2 ± 10.2.8
- Clearance
Adapalene is rapidly cleared from blood plasma, typically undetectable after 72 hours following topical application.8
- 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
Toxicity information regarding adapalene is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as redness, scaling, and skin discomfort. Symptomatic and supportive measures are recommended.8
Adapalene has an acute oral LD50 in S-D rats and CD-1 mice of over 5000 mg/kg. The LD50 of 0.3% applied topically to Credo OF1 mice is over 10 ml/kg (30 mg/kg). No systemic or local toxicity was observed in rats treated topically with 6 mg/kg/day of 0.3% adapalene.9
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareResorcinol The risk or severity of adverse effects can be increased when Resorcinol is combined with Adapalene. Salicylic acid The risk or severity of adverse effects can be increased when Salicylic acid is combined with Adapalene. - 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
- Adaferin / Differine
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Differin Liquid 0.1 % Topical Galderma 2001-08-08 2003-07-08 Canada 
Differin Cream 1 mg/1g Topical Physicians Total Care, Inc. 2005-04-19 Not applicable US 
Differin Gel 0.1 % Topical Galderma 1996-12-31 Not applicable Canada Differin Lotion 0.1 g/100mL Topical Galderma Laboratories, L.P. 2010-03-31 2025-12-31 US Differin Gel 3 mg/1g Topical Physicians Total Care, Inc. 2008-10-24 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Adapalene Cream 1 mg/1g Topical bryant ranch prepack 2010-06-30 Not applicable US Adapalene Cream 1 mg/1g Topical Physicians Total Caer, Inc. 2010-10-01 Not applicable US Adapalene Gel 1 mg/1g Topical A-S Medication Solutions 2010-07-01 Not applicable US Adapalene Solution 1 mg/1mL Topical Allegis Pharmaceuticals, LLC 2018-08-20 2019-12-31 US Adapalene Gel 1 mg/1g Topical A-S Medication Solutions 2010-06-02 2016-12-31 US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Adapalene Gel 1 mg/1g Topical Stryke Club, Inc. 2021-11-12 2024-12-31 US Adapalene Gel 1 mg/1g Topical CVS Pharmacy, Inc 2023-10-31 Not applicable US Adapalene Gel 1 mg/1g Topical CVS PHARMACY 2019-08-01 Not applicable US Adapalene Gel 1 mg/1g Topical TARGET Corporation 2021-11-01 2023-12-31 US Adapalene Gel 1 mg/1g Topical Walgreens 2023-10-25 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Adapalene and benzoyl peroxide Adapalene (3 mg/1g) + Benzoyl peroxide (25 mg/1g) Gel Topical Viona Pharmaceuticals Inc 2022-06-06 Not applicable US Adapalene and Benzoyl Peroxide Adapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g) Gel Topical Prasco, Laboratories 2017-08-03 Not applicable US Adapalene and Benzoyl Peroxide Adapalene (3 mg/1g) + Benzoyl peroxide (25 mg/1g) Gel Topical Taro Pharmaceuticals U.S.A., Inc. 2018-10-17 Not applicable US Adapalene and Benzoyl Peroxide Adapalene (3 mg/1g) + Benzoyl peroxide (25 mg/1g) Gel Topical Mayne Pharma Inc. 2022-02-01 Not applicable US Adapalene and Benzoyl Peroxide Adapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g) Gel Topical Sandoz Inc. 2018-05-23 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Adapalene 0.1% / Benzoyl Peroxide 2.5% / Clindamycin 1% Adapalene (0.1 g/100g) + Benzoyl peroxide (2.5 g/100g) + Clindamycin phosphate (1 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-10 Not applicable US Adapalene 0.1% / Benzoyl Peroxide 2.5% / Niacinamide 4% Adapalene (0.1 g/100g) + Benzoyl peroxide (2.5 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-10 Not applicable US Adapalene 0.3% / Benzoyl Peroxide 2.5% / Clindamycin 1% Adapalene (0.3 g/100g) + Benzoyl peroxide (2.5 g/100g) + Clindamycin phosphate (1 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-01 Not applicable US Adapalene 0.3% / Benzoyl Peroxide 2.5% / Niacinamide 4% Adapalene (0.3 g/100g) + Benzoyl peroxide (2.5 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-01 Not applicable US Adapalene 0.3% / Niacinamide 4% Adapalene (0.3 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-10 Not applicable US
Categories
- ATC Codes
- D10AD03 — Adapalene
- D10AD — Retinoids for topical use in acne
- D10A — ANTI-ACNE PREPARATIONS FOR TOPICAL USE
- D10 — ANTI-ACNE PREPARATIONS
- D — DERMATOLOGICALS
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Prenol lipids
- Sub Class
- Retinoids
- Direct Parent
- Retinoids
- Alternative Parents
- Phenylnaphthalenes / Naphthalenecarboxylic acids / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
- Substituents
- 2-naphthalenecarboxylic acid / 2-naphthalenecarboxylic acid or derivatives / Adapalene / Alkyl aryl ether / Anisole / Aromatic homopolycyclic compound / Benzenoid / Carboxylic acid / Carboxylic acid derivative / Ether
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- monocarboxylic acid, adamantanes (CHEBI:31174)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1L4806J2QF
- CAS number
- 106685-40-9
- InChI Key
- LZCDAPDGXCYOEH-UHFFFAOYSA-N
- InChI
- InChI=1S/C28H28O3/c1-31-26-7-6-23(21-2-3-22-12-24(27(29)30)5-4-20(22)11-21)13-25(26)28-14-17-8-18(15-28)10-19(9-17)16-28/h2-7,11-13,17-19H,8-10,14-16H2,1H3,(H,29,30)
- IUPAC Name
- 6-[3-(adamantan-1-yl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
- SMILES
- COC1=C(C=C(C=C1)C1=CC2=C(C=C1)C=C(C=C2)C(O)=O)C12CC3CC(CC(C3)C1)C2
References
- Synthesis Reference
Graziano Castaldi, Pietro Allegrini, Gabriele Razzetti, Mauro Ercoli, "Process for the preparation of adapalene." U.S. Patent US20060229465, issued October 12, 2006.
US20060229465- General References
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [Article]
- Shroot B: Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol. 1998 Aug;39(2 Pt 3):S17-24. doi: 10.1016/s0190-9622(98)70440-2. [Article]
- Zaenglein AL: Acne Vulgaris. N Engl J Med. 2018 Oct 4;379(14):1343-1352. doi: 10.1056/NEJMcp1702493. [Article]
- Grosshans E, Marks R, Mascaro JM, Torras H, Meynadier J, Alirezai M, Finlay AY, Soto P, Poncet M, Verschoore M, Clucas A: Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life. Br J Dermatol. 1998 Oct;139 Suppl 52:26-33. doi: 10.1046/j.1365-2133.1998.1390s2026.x. [Article]
- Leyden JJ, Wortzman M, Baldwin EK: Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide cleanser 6%. Cutis. 2008 Dec;82(6):417-21. [Article]
- Beckenbach L, Baron JM, Merk HF, Loffler H, Amann PM: Retinoid treatment of skin diseases. Eur J Dermatol. 2015 Sep-Oct;25(5):384-91. doi: 10.1684/ejd.2015.2544. [Article]
- FDA Approved Drug Products: Differin (adapalene) gel [Link]
- FDA: Pharmacology/Toxicology Review and Evaluation (adapalene) [Link]
- DPD Monograph: Differin (adapalene) topical cream/gel/lotion [Link]
- FDA Approved Drug Products: Epiduo (adapalene and benzoyl peroxide), gel [Link]
- INVIMA Product Authorization: Clinacyin (adapalene/clindamycin phosphate) topical gel [Link]
- FDA Approved Drug Products: Cabtreo (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel [Link]
- External Links
- Human Metabolome Database
- HMDB0014355
- KEGG Drug
- D01112
- PubChem Compound
- 60164
- PubChem Substance
- 46505019
- ChemSpider
- 54244
- BindingDB
- 50048280
- 60223
- ChEBI
- 31174
- ChEMBL
- CHEMBL1265
- ZINC
- ZINC000003784182
- Therapeutic Targets Database
- DAP000115
- PharmGKB
- PA448047
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Adapalene
- FDA label
- Download (25.9 KB)
- MSDS
- Download (57.1 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 Active Not Recruiting Treatment Acne Vulgaris 1 somestatus stop reason just information to hide Not Available Completed Not Available Acne 1 somestatus stop reason just information to hide Not Available Completed Not Available Acne Vulgaris 2 somestatus stop reason just information to hide Not Available Completed Treatment Acne Vulgaris 4 somestatus stop reason just information to hide Not Available Completed Treatment Acne Vulgaris / Diet Modification 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Nycomed us inc
- Galderma laboratories lp
- Glenmark generics inc usa
- Pliva hrvatska doo
- Galderma research and development inc
- Galderma Laboratories
- Packagers
- Ameri-Pac Inc.
- DPT Laboratories Ltd.
- E. Fougera and Co.
- Galderma Laboratories
- Glenmark Generics Ltd.
- Lake Erie Medical and Surgical Supply
- Physicians Total Care Inc.
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Cream Cutaneous 0.100 g Gel Cutaneous 0.300 g Cream Topical 0.1 g/100g Cream Topical 1 mg/1g Gel Topical 0.1 g/1g Gel Topical 1 mg/1g Gel Topical 45 g/1g Lotion Topical .1 g/100mL Gel Topical 0.00036 g/1g Swab Topical 1 mg/1mL Cream Topical 1 MG/G Gel Gel Topical 0.100 g Kit Topical Gel Cutaneous 0.1 % w/w Gel Topical 1.00 mg/g Cream Topical Cream Topical 0.1 % Gel Topical Gel Topical 0.1 % Gel Topical 0.1 %w/w Gel Topical 3 mg/1g Liquid Topical 0.1 % Lotion Topical 0.1 % Lotion Topical 0.1 g/100mL Lotion Topical 1 mg/1g Solution Topical 1 mg/1mL Gel Topical 1 mg/g Cream Cutaneous 0.1 % Gel Topical 0.1 % w/w Gel Topical 0.3 % Gel Topical Gel Cutaneous Gel Topical 0.10 % Cream 0.1 % w/w Gel Topical 0.1 MG/G Solution Topical Gel Cutaneous 0.100 g Gel Cutaneous 1.000 MG Cream Gel Topical 0.1 g/100g Gel Cutaneous 0.1 % Gel Cutaneous 110.000 mg Cream Topical 0.3 g Gel Cutaneous 0.100 g Cream Topical Cream Topical 0.1 g Gel Topical 0.3 g Gel Topical 0.1 g - Prices
Unit description Cost Unit Differin 0.1% Cream 45 gm Tube 227.13USD tube Differin 0.1% Gel 45 gm Tube 227.13USD tube Differin 0.3% Gel 45 gm Tube 219.65USD tube Differin 0.1% cream 4.85USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US4717720 No 1988-01-05 2010-05-31 US US8909305 No 2014-12-09 2022-12-23 US US7579377 No 2009-08-25 2025-02-23 US US7834060 No 2010-11-16 2023-03-12 US US7868044 No 2011-01-11 2023-03-12 US US8703820 No 2014-04-22 2023-03-12 US US7838558 No 2010-11-23 2023-03-12 US US7737181 No 2010-06-15 2024-08-29 US US7964202 No 2011-06-21 2024-09-01 US US8071644 No 2011-12-06 2027-07-18 US US8080537 No 2011-12-20 2027-07-18 US US8105618 No 2012-01-31 2022-12-23 US US8129362 No 2012-03-06 2027-07-18 US US8445543 No 2013-05-21 2027-07-12 US US8809305 No 2014-08-19 2022-12-23 US US8936800 No 2015-01-20 2022-12-23 US US8241649 No 2012-08-14 2022-12-23 US US7820186 No 2010-10-26 2025-11-23 US US7998467 No 2011-08-16 2028-05-31 US US8435502 No 2013-05-07 2026-09-15 US US8709392 No 2014-04-29 2026-09-15 US US8288434 No 2012-10-16 2029-08-05 US US8785420 No 2014-07-22 2022-12-23 US US8729127 No 2014-05-20 2023-03-12 US US9561208 No 2017-02-07 2029-06-03 US US9381179 No 2016-07-05 2023-03-12 US US9387187 No 2016-07-12 2023-03-12 US US9814690 No 2017-11-14 2022-12-23 US US10220049 No 2019-03-05 2029-06-03 US US10624918 No 2020-04-21 2029-06-03 US US11389467 No 2020-12-28 2040-12-28 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 300 http://datasheets.scbt.com/sds/aghs/en/sc-203803.pdf boiling point (°C) 606.3 http://datasheets.scbt.com/sds/aghs/en/sc-203803.pdf logP 6.917 http://www.chemspider.com/Chemical-Structure.54244.html?rid=2edd1b0e-994a-4cdc-870c-186c62dcad5a&page_num=0 - Predicted Properties
Property Value Source Water Solubility 4.01e-06 mg/mL ALOGPS logP 6.06 ALOGPS logP 6.46 Chemaxon logS -8 ALOGPS pKa (Strongest Acidic) 3.99 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 46.53 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 122.07 m3·mol-1 Chemaxon Polarizability 47.64 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.7061 Caco-2 permeable + 0.8439 P-glycoprotein substrate Non-substrate 0.5408 P-glycoprotein inhibitor I Non-inhibitor 0.8074 P-glycoprotein inhibitor II Inhibitor 0.5 Renal organic cation transporter Non-inhibitor 0.8646 CYP450 2C9 substrate Non-substrate 0.7171 CYP450 2D6 substrate Non-substrate 0.8925 CYP450 3A4 substrate Non-substrate 0.5116 CYP450 1A2 substrate Non-inhibitor 0.7812 CYP450 2C9 inhibitor Inhibitor 0.7758 CYP450 2D6 inhibitor Non-inhibitor 0.9466 CYP450 2C19 inhibitor Non-inhibitor 0.653 CYP450 3A4 inhibitor Non-inhibitor 0.8246 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8509 Ames test Non AMES toxic 0.8575 Carcinogenicity Non-carcinogens 0.8707 Biodegradation Not ready biodegradable 0.9715 Rat acute toxicity 2.6913 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9774 hERG inhibition (predictor II) Non-inhibitor 0.8855
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0002-0009000000-2169879160d27fbd36e2 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03dj-0007900000-4540fcb1238e572212f0 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0009100000-e9304e5df484ede40306 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014s-0409100000-0697c98c4659d454b299 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-02t9-0009300000-f34de78568b070b07902 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0397100000-1ad7da90607ba351d455 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0209000000-1f3833fabdf9eb89fa6a Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 222.8647212 predictedDarkChem Lite v0.1.0 [M-H]- 197.47966 predictedDeepCCS 1.0 (2019) [M+H]+ 223.7184212 predictedDarkChem Lite v0.1.0 [M+H]+ 199.87521 predictedDeepCCS 1.0 (2019) [M+Na]+ 223.4540212 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.78773 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
- General Function
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (PubMed:12554770). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (PubMed:29021580). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity)
- Specific Function
- Dna binding
- Gene Name
- RARB
- Uniprot ID
- P10826
- Uniprot Name
- Retinoic acid receptor beta
- Molecular Weight
- 50488.63 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
- General Function
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity)
- Specific Function
- Chromatin binding
- Gene Name
- RARG
- Uniprot ID
- P13631
- Uniprot Name
- Retinoic acid receptor gamma
- Molecular Weight
- 50341.405 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- 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
- Curator comments
- Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
- General Function
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE)
- Specific Function
- Dna-binding transcription activator activity, rna polymerase ii-specific
- Gene Name
- RXRB
- Uniprot ID
- P28702
- Uniprot Name
- Retinoic acid receptor RXR-beta
- Molecular Weight
- 56921.38 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
- General Function
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity)
- Specific Function
- Dna-binding transcription factor activity, rna polymerase ii-specific
- Gene Name
- RXRG
- Uniprot ID
- P48443
- Uniprot Name
- Retinoic acid receptor RXR-gamma
- Molecular Weight
- 50870.72 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
- General Function
- Receptor for retinoic acid that acts as a transcription factor (PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:37478846, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632)
- Specific Function
- Dna binding domain binding
- Gene Name
- RXRA
- Uniprot ID
- P19793
- Uniprot Name
- Retinoic acid receptor RXR-alpha
- Molecular Weight
- 50810.835 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Adapalene, likely through binding to RARs/RXRs, exerts a transrepressive effect on AP-1 activity.
- General Function
- Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity (By similarity). Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (PubMed:12618758). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306)
- Specific Function
- Camp response element binding
- Gene Name
- JUN
- Uniprot ID
- P05412
- Uniprot Name
- Transcription factor Jun
- Molecular Weight
- 35675.32 Da
References
- Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [Article]
- Lefebvre P, Martin PJ, Flajollet S, Dedieu S, Billaut X, Lefebvre B: Transcriptional activities of retinoic acid receptors. Vitam Horm. 2005;70:199-264. doi: 10.1016/S0083-6729(05)70007-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Adapalene down-regulates TLR-2 expression in a dose-dependent manner.
- General Function
- Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:17889651, PubMed:21078852). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6 (PubMed:11441107). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression (PubMed:15809303). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (PubMed:16880211). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By similarity)
- Specific Function
- Amyloid-beta binding
- Gene Name
- TLR2
- Uniprot ID
- O60603
- Uniprot Name
- Toll-like receptor 2
- Molecular Weight
- 89836.575 Da
References
- Tenaud I, Khammari A, Dreno B: In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol. 2007 Jun;16(6):500-6. doi: 10.1111/j.1600-0625.2007.00552.x. [Article]
- Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
- General Function
- Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:28167758, PubMed:37478846, PubMed:21152046). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:9267036, PubMed:37478846). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758)
- Specific Function
- Alpha-actinin binding
- Gene Name
- RARA
- Uniprot ID
- P10276
- Uniprot Name
- Retinoic acid receptor alpha
- Molecular Weight
- 50770.805 Da
References
- Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [Article]
- Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [Article]
- Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [Article]
- Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway (PubMed:27827456)
- Specific Function
- L-aspartate
- Gene Name
- GOT1
- Uniprot ID
- P17174
- Uniprot Name
- Aspartate aminotransferase, cytoplasmic
- Molecular Weight
- 46247.14 Da
References
- Wang Q, Zhang Q, Luan S, Yang K, Zheng M, Li K, Chen L, Li H: Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. Bioorg Chem. 2019 Dec;93:103315. doi: 10.1016/j.bioorg.2019.103315. Epub 2019 Sep 26. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 01:12