2. Academic Validation
  3. Discovery of an ITK and TRK kinase inhibitor for the potential topical treatment of atopic dermatitis

Discovery of an ITK and TRK kinase inhibitor for the potential topical treatment of atopic dermatitis

  • Nat Commun. 2026 Mar 9. doi: 10.1038/s41467-026-70000-6.
Jennifer L Duffen 1,  Kimberly K Crouse 2,  Lin Ji 2,  Amy L Brault 3,  Kristen Ford 3,  Jonathan Brooks 2,  Scott A Jelinsky 2,  Yizheng Li 2,  Julia H Shin 2,  Yajuan Zhao 2,  Tatyana Andreyeva 2,  Katherine Hammerman 4,  Christina Arnold 2,  Richard T Sheldon 2,  Jeonifer Garren 5,  Wes LaBarge 6,  Anthony Resek 6,  Jon Volmer 6,  Scott W Bagley 3,  Agustin Casimiro-Garcia 7,  Gary M Chinigo 3,  Jennifer E Davoren 7,  Rajiah Aldrin Denny 7,  Susan Drozda 3,  Timothy L Foley 3,  Robert W Hicklin 3,  Shenping Liu 3,  Frank E Lovering 7,  Nicole L Nedoma 3,  Mihir D Parikh 3,  Joseph W Strohbach 7,  John I Trujillo 3,  Stefanus J Steyn 8,  Karl Nocka 2,  Martin Hegen 2,  Fabien Vincent 3,  Katherine L Lee 2,  Brian S Gerstenberger 9,  Michael J Primiano 2
Affiliations

Affiliations

  • 1 Inflammation and Immunology, Pfizer Inc, Cambridge, MA, USA. Jennifer.Duffen@pfizer.com.
  • 2 Inflammation and Immunology, Pfizer Inc, Cambridge, MA, USA.
  • 3 Medicine Design, Pfizer Inc, Groton, CT, USA.
  • 4 Drug Safety Research and Development, Pfizer Inc, Cambridge, MA, USA.
  • 5 Data Sciences and Analytics, Pfizer Inc, Cambridge, MA, USA.
  • 6 MedPharm Ltd, Durham, NC, USA.
  • 7 Medicine Design, Pfizer Inc, Cambridge, MA, USA.
  • 8 Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc, Cambridge, MA, USA.
  • 9 Medicine Design, Pfizer Inc, Cambridge, MA, USA. Brian.Gerstenberger@pfizer.com.
PMID: 41803126 DOI: 10.1038/s41467-026-70000-6
Abstract

Interleukin-2-inducible T cell kinase is expressed by T cells and amplifies T cell receptor-dependent signals. Interleukin-2-inducible T cell kinase deletion or inhibition reduces production of interleukin-4 and interleukin-13, key drivers of atopic dermatitis. Nerve growth factor signals via the receptor tropomyosin-related kinase A and may promote pruritus in atopic dermatitis lesions. Here we describe PF-07245303, a compound which potently inhibits interleukin-2-inducible T cell kinase and tropomyosin-related kinase family kinases capable of inhibiting T cell receptor-mediated cytokine production from CD4 and CD8 T cells and suppressing nerve growth factor-induced human basophil activation. In human skin explants, PF-07245303 demonstrates inhibition of tropomyosin-related kinase A phosphorylation, suppresses cytokine expression from T cell receptor-activated resident T cells and reverses the expression of atopic dermatitis associated genes. Topical application of PF-07245303 reduces proinflammatory and epidermal changes in a dermatitis model using female mice. By inhibiting both pathogenic inflammatory mechanisms, PF-07245303 may have therapeutic value for patients with atopic dermatitis.

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