Tapinarof is a synthetic, small-molecule aryl hydrocarbon receptor (AhR) agonist used as a topical pharmaceutical active ingredient. It is marketed in the United States as VTAMA. FDA describes Tapinarof as a white to pale-brown powder with the molecular formula C17H18O2 and molecular weight 254.32 g/mol.
Tapinarof is also known as Benvitimod, WBI-1001, and GSK2894512. FDA's substance registry identifies Tapinarof under UNII 84HW7D0V04, while PubChem lists CAS 79338-84-4.
Tapinarof is chemically known as 3,5-dihydroxy-4-isopropyl-trans-stilbene, also described as (E)-2-isopropyl-5-styrylbenzene-1,3-diol. It contains a trans-configured double bond and has no chiral centers. FDA's chemistry review reports that the trans configuration was established by single-crystal X-ray crystallography and that multiple anhydrous crystalline forms have been identified.
The molecule contains two phenolic hydroxyl groups and an isopropyl-substituted stilbene structure. These structural characteristics contribute to its relatively high lipophilicity and low aqueous solubility.
Tapinarof acts as an aryl hydrocarbon receptor agonist. Activation of AhR influences transcriptional pathways involved in immune and inflammatory responses. In dermatological applications, this mechanism contributes to modulation of inflammatory pathways associated with psoriasis and atopic dermatitis.
Tapinarof was initially approved by the FDA for the topical treatment of plaque psoriasis in adults. Current U.S. labeling also covers the topical treatment of atopic dermatitis in adults and pediatric patients 2 years of age and older.
The marketed VTAMA formulation contains 10 mg of Tapinarof per gram of cream, corresponding to a 1% topical formulation.
Tapinarof is a white to pale-brown powder with a molecular weight of 254.32 g/mol. FDA's drug-substance assessment classifies it as practically insoluble in water, ≤0.1 mg/mL, while reporting that it is freely soluble in methanol, ethanol and acetone at concentrations above 200 mg/mL.
Published commercial/reference data report melting ranges around 140–150°C, with TCI reporting 146–150°C for its reference material. Because these values differ among sources and solid forms, they should be treated as physical/reference characteristics rather than automatically used as a registered API release limit.
Tapinarof drug substance requires control of identity, assay, related substances, residual solvents, water content and solid-state characteristics. FDA's chemistry review states that the proposed drug-substance specification adequately addressed critical attributes affecting the quality of the drug product.
FDA also reports that the molecular structure was characterized using single-crystal X-ray diffraction, powder X-ray diffraction, NMR, mass spectrometry and infrared spectroscopy.
Tapinarof is a chemically synthesized small-molecule API. Manufacturing requires control of the trans-stilbene configuration, crystalline form, reaction-related impurities, residual solvents and final drug-substance quality attributes.
FDA's CMC assessment found the manufacturing process and control strategy adequate for registration and commercial batches.
Tapinarof API should be packaged in suitable pharmaceutical-grade, well-closed containers and protected from moisture, contamination and excessive environmental exposure. Storage should follow validated stability data and the applicable registered API specification.
A pharmaceutical-grade Tapinarof API package may include a Certificate of Analysis, specification sheet, analytical methods, impurity profile, residual-solvent data, stability information, safety documentation and applicable regulatory documentation.
A qualified Tapinarof API manufacturer in India should maintain strong controls over identity, assay, related substances, residual solvents, water content and crystalline form. Consistent control of these attributes is important for reliable manufacture of topical pharmaceutical formulations containing Tapinarof.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Melting Point | 146–150°C |