Mohd Jamal Dar, PhD
Professor, AcSIR (Biological Sciences)
Jammu, J&K-180001 India

 

Discovery of  novel JAK3 specific  small molecule inhibitor involved in promoting hair regrowth

11/07/2024 – ore 14:00

 

Abstract: 

Alopecia areata is an autoimmune disease that occurs when the immune system attacks hair follicles and causes them to lose the ability to enter the growth phase of the hair growth cycle, ultimately resulting in hair loss. Hair follicles were previously thought to be missing from the areas of complete baldness, however, recent studies have shown that even the bald areas of the human scalp contain hair follicles and hair follicle stem cells. Recently, pharmacological inhibition of JAK-STAT signaling was seen to enhance hair re-growth by awakening quiescent hair follicle stem cells (HFSCs). Thus, JAK-STAT signalling pathway has emerged as a promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 is an ideal target for drug discovery because it only regulates a narrow spectrum of gc cytokines. In a recent study, we reported the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter. During in-vivoefficacy assays, topical application of MJ04 on DHT-challenged AGA mice and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04exhibited a reasonably good pharmacokinetic profile and demonstrated a favorable safety profile under in-vivo and in-vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.

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