biostudies-literatureHossain MMHuman Resource Development Centre, Council of Scientific And Industrial Research370https://www.ebi.ac.uk/biostudies/studies/S-EPMC11025159biostudies-literatureUnknown22(1)JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC₅₀ of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA 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. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under iJournal of translational medicineDiscovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter.PMC11025159MLP 110007HCP-40Ahmed ZRamajayan PBhat AQKumar MAkhter ZKhalid AKeshari PHussain RAhmed FParveen SDhiman SNandi USingh UMustafa GShowket FGupta SDar MSNargorta AHossain MMYadav GSingh PPKshatri ASAyaz MOMir RABadesra NKhan NTaneja NDar MJfalseDiscovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter.JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC₅₀ of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA 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. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under i2024-01-01T00:00:00Z2024 Apr2026-06-01T09:19:47.946Z2026-04-08T11:03:25.066ZS-EPMC110251593863784210.1186/s12967-024-05144-4