Trifarotene
JFDA label: AKLIEF 50mcg/g Cream
Mechanism of Action
Agonist of Retinoic acid receptor gamma — Retinoic acid receptor gamma agonist
| Target | Action | Gene / class |
|---|---|---|
| Retinoic acid receptor gamma efficacy | AGONIST | RARG |
Indications
Approved
- Acne Vulgaris — acne
Off-label
- Ichthyosis, Lamellar
Contraindications
Source: openFDA
- None None ( 4 ) Absolute
Adverse Reactions
Skin and subcutaneous tissue disorders (1)
Common For The Entire Trial Were Application Site Pruritus
General disorders and administration site conditions (2)
Common And Sunburn · Application Site Irritation
Dosing
Source: openFDA
Warnings & Precautions
Source: openFDA
Warnings & Precautions
Skin irritation: Erythema, scaling, dryness, and stinging/burning may be experienced with use of AKLIEF Cream. Use a moisturizer from the initiation of treatment, and, if appropriate, reduce the frequency of application of AKLIEF Cream, suspend or discontinue use. ( 5.1 ) Ultraviolet Light and Environmental Exposure: Minimize exposure to sunlight and sunlamps. Use sunscreen and protective clothing over treated areas when exposure cannot be avoided. ( 5.2 )
Skin Irritation Patients using AKLIEF Cream may experience erythema, s
Skin Irritation Patients using AKLIEF Cream may experience erythema, scaling, dryness, and stinging/burning. Maximum severity of these reactions typically occurred within the first 4 weeks of treatment, and severity decreased with continued use of the medication. Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of application of AKLIEF Cream, or suspend use temporarily. If severe reactions persist the treatment may be discontinued. Avoid application of AKLIEF Cream to cuts, abrasions, or eczematous or sunburned skin. Use of “waxing” as a depilatory method should be avoided on skin treated with AKLIEF Cream.
Ultraviolet Light and Environmental Exposure Minimize unprotected expo
Ultraviolet Light and Environmental Exposure Minimize unprotected exposure to ultraviolet rays (including sunlight and sunlamps) during treatment with AKLIEF Cream. Warn patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided.
Pregnancy & Lactation
Lactation
Because it is poorly absorbed after topical application, it is a low risk to the nursing infant.
Chemistry & Properties
| Formula | C29H33NO4 |
|---|---|
| Molecular weight | 459.59 g/mol |
| IUPAC name | 4-[3-(3-tert-butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid |
| CAS | 895542-09-3 |
| PubChem CID | 11518241 |
| InChIKey | MFBCDACCJCDGBA-UHFFFAOYSA-N |
| logP | 5.99 (XLogP 6.3) |
| Polar surface area | 70.0 Ų |
| H-bond acceptors / donors | 4 / 2 |
| Drug-likeness (QED) | 0.45 |
| Lipinski violations | 1 |
SMILES
CC(C)(C)c1cc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCO)ccc1N1CCCC1Biology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 1.225 h |
| Volume of distribution | 0.416 L/kg |
| Protein binding | 98.3% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2B6 | Inhibitor | — |
| CYP2B6 | Substrate | — |
| CYP2C19 | Inhibitor | — |
| CYP2C8 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 3)
| Target | Action | Affinity |
|---|---|---|
| Retinoic acid receptor-γ (RARG) | Agonist | pEC50 8.1 |
| Retinoic acid receptor-β (RARB) | Agonist | pEC50 6.9 |
| Retinoic acid receptor-α (RARA) | Agonist | pEC50 6.3 |
Transporters
BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Registered Products (1)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| AKLIEF 50mcg/g Cream | Cream 50 mcg/1 g | 75 GM Pump | IBN CINA DRUG STORE | 32.560 |