Fig. 1

Identification of MJ04 as JAK3 inhibitor and its biological characteristics. A The chemical structure of compound MJ04. B Inhibitory activity and selectivity of MJ04 for JAK family kinases at Km and 1 mM ATP concentration. C The IC50 of MJ04 and tofacitinib inhibiting JAK3 at Km ATP concentration. D The inhibitory potency and selectivity of MJ04 against a panel of 10 kinases at Km ATP concentration. E Intermolecular interactions of MJ04 with JAK1 (3EYG), JAK2 (6TPD) and JAK3 (5WFJ) kinase domain: E (a) Multiple sequence alignment of JAK1, JAK2 and JAK3 with conserved regions labelled as G loop (glycine rich loop, L881-E890-JAK1, L855-E864-JAK2, L828-E837-JAK3), hinge region (M956-L968-JAK1, M929-L941-JAK2, M902-L914-JAK3) catalytic loop (H1001-L1010-JAK1, H974-L981-JAK2, H947-L956-JAK3) and A loop (activation loop, D1021-E1051-JAK1, D994-E1024-JAK2, D967E997-JAK3) indicating the conserved residues in each region. E (b) represents the superimposed structure of JAK1, JAK2 and JAK3 with inhibitor molecule MJ04 present in the hinge region and different regions are coloured and labelled as hinge region (hot pink), catalytic loop (orange), activation loop (blue) and glycine rich loop (cyan), the E (c), E (d) and E (e) is representing the enlarged view of intermolecular interactions of MJ04 with JAK1, JAK2 and JAK3 respectively with inhibitor MJ04 in stick coloured in red and heteroatoms coloured differently, hydrophobic interacting residues in wire and magenta colour and hydrogen bonding residues in stick coloured in yellow with heteroatoms differently coloured, H-bonds are represented as red coloured dotted lines with length labelled