Small molecule inhibitors and inflammatory skin diseases

Abstract EN

Inflammatory skin diseases (ISDs) are originally a consequence of many processes of protective and regenerative skin responses against infections and dangers.

A characteristic feature of each ISD is the production of disease-relevant cytokines by local immune and epithelial cells.

The JAK-STAT pathway is necessary for a wide range of cytokines and growth factors, leading to critical cellular events.

Cytokines that signal through type I/II cytokine receptors typically activate at least one JAK family member and one or more STAT proteins.

Many of immunological disorders have been happened through different cytokine receptors throughout the JAK-STAT pathway, particularly T cell mediated diseases.

Thus, targeting of this pathway has gained huge attraction.

New drugs were introduced to inhibit JAK and STAT molecules.

Although only few JAK inhibitors (JAKinib) are FDA approved, other JAKinibs and possible STAT inhibitors are being developed by passing preclinical evaluations and clinical trials.

For example, the oral JAK1/JAK2 inhibitors ruxolitinib and baricitinib both seem to induce hair-regrowth in patients with Alopecia areata.

The tofacitinib, (JAK1/JAK3 inhibitor) showed an improvement of >75% of the psoriasis area.

the first generation which targeting multiple JAK/STAT-associated cytokines at the same time as the second generation which targeting the signaling pathway itself is an alternative approach to neutralizing single cytokines by antibodies.