Development of PAC-14028, a novel transient receptor potential vanilloid type 1 (TRPV1) channel antagonist as a new drug for refractory skin diseases

The transient receptor potential vanilloid 1 (TRPV1) is a member of nonselective cation channels and has been implicated in the progression of neurogenic inflammation and nociception. Through the synthesis of over 2,000 new compounds, a novel non-vanilloid TRPV1 Antagonist PAC-14028 was discovered. As well as ideal physicochemical and pharmacokinetic properties, PAC-14028 showed meaningful efficacies against diverse disease models that include visceral Pain, Inflammatory Bowel Disease, and inflammatory Pain. Of note, PAC-14028 effectively attenuates Atopic Dermatitis and pruritus without significant adverse effects, which is a substantial benefit over conventional pharmacotherapy. This report introduces the potential of a novel TRPV1 Antagonist PAC-14028 as a new drug for Atopic Dermatitis and pruritus.