| Candidate ID: | R0079 |
| Source ID: | DB00210 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Adapalene
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| Synonyms: |
6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid; Adapalene
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| Molecular Formula: |
C28H28O3
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| SMILES: |
COC1=C(C=C(C=C1)C1=CC2=C(C=C1)C=C(C=C2)C(O)=O)C12CC3CC(CC(C3)C1)C2
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| Structure: |
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| DrugBank Description: |
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. Adapalene has similar efficacy but a superior safety profile compared to tretinoin. is more efficacious than adapalene but is designated as pregnancy category X and hence is contraindicated in pregnant women. Adapalene can also be combined with benzoyl peroxide (BPO), which possesses bactericidal properties, and either adapalene alone, or adapalene BPO combination products, are commonly used to treat mild-to-severe acne.
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.
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| CAS Number: |
106685-40-9
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| Molecular Weight: |
412.5201
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| DrugBank Indication: |
Adapalene is indicated for the topical treatment of acne vulgaris in patients aged 12 and over.
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| DrugBank Pharmacology: |
Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. 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.
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| DrugBank MoA: |
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. Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. 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.
When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.
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| Targets: |
Retinoic acid receptor beta agonist; Retinoic acid receptor gamma agonist; Retinoic acid receptor RXR-beta agonist; Retinoic acid receptor RXR-gamma agonist; Retinoic acid receptor RXR-alpha agonist; Transcription factor AP-1 antagonist; Toll-like receptor 2 antagonist; Retinoic acid receptor alpha; Aspartate aminotransferase, cytoplasmic inhibitor
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| Inclusion Criteria: |
Therapeutic strategy associated
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