Tapinarof

Tapinarof is a first-in-class topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of mild to moderate plaque psoriasis in adults, and represents the first non-steroidal topical therapy with a novel mechanism of action in this indication in over 25 years . As a small-molecule stilbene derivative, Tapinarof exhibits diverse biological activities, including antifungal properties against Candida tropicalis, Cryptococcus neoformans, and Aspergillus fumigatus . The AhR agonist activity of Tapinarof has been validated in both preclinical and clinical studies, demonstrating its ability to resolve skin inflammation by reducing IL-17A expression in keratinocytes and modulating the immune response . In pharmaceutical quality control contexts, Tapinarof and its related substances serve as essential reference standards for analytical method development, impurity profiling, and regulatory submissions. The unique structural features of Tapinarof — particularly the stilbene core combined with the resorcinol moiety — provide a rigid, planar scaffold that facilitates high-affinity binding to AhR, making this compound a valuable tool in dermatological drug discovery and a benchmark for developing next-generation AhR-targeting therapeutics .

Product Parameters

Application

Tapinarof (brand name: Vtama), also known as GSK2894512, was discovered by GlaxoSmithKline and licensed to Dermavant Sciences (a subsidiary of Riovant Chemical Book Sciences) in 2020. Tapinarof is an innovative, topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis in adults.

Synthetic Route

The synthesis of benenemod begins with the aldol condensation of cinnamaldehyde (14.1) and ketone 14.2, yielding the α,β,γ,δ-unsaturated ketone 14.3. Cinnamaldehyde (14.1) is converted to ketone 14.4 via Michael addition with diethyl malonate, with a yield of 62%. Hydrolysis of 14.4 yields the malonic acid derivative 14.5. Treatment of 14.5 with a base at high temperature induces the decarboxylation of the malonic acid molecule. Subsequently, under acidic conditions, a methyl ester is formed, followed by a Claisen condensation reaction to obtain the cyclic diketone 14.6, with a combined overall yield of 79% across these three steps. Chlorination of 14.6 using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) yields the penultimate intermediate enantiomeric mixture 14.7, with a yield of 96%. Treatment of the cyclic chlorodiketone 14.7 with tetraethyl chloride yields benenemod 14, with a yield of 86%.

Bioactivity

Tapinarof (GSK2894512, Benvitimod, WBI1001, DHPS, DMVT505) is a natural ligand for the arylhydrocarbon receptor (AhR) that can induce nuclear translocation of AhR in immortalized keratinocytes (HaCaT), with an EC₅₀ value of 0.16 nM. Tapinarof also induces apoptosis in CD⁴⁺T cells in a dose-dependent manner, with an IC₅₀ value of 5.2 μM.

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Your search for a reliable Tapinarof supply partner — whether for API manufacturing, reference standard requirements, or drug development programs — should be straightforward. At Cosperpharm, we combine scientific excellence, regulatory expertise, and supply chain reliability to deliver the quality you need, precisely when you need it. Contact our customer service team today to discuss your specific requirements, request a quotation, or schedule a technical consultation.