Like folic acid, folate antagonist therapeutic drugs such as methotrexate (MTX, the anchor drug in RA treatment) (53, 54) and pemetrexed (PMX) (55) share a pterin moiety in their structure which can bind in the hydrophobic region of the binding pocket of FRβ (52) (Figure 1D). Here, FOLR2 is linked to rheumatoid arthritis.