2.A.57.1.1
Equilibrative nucleoside transporter (ENT1) (present in the membranes surrounding the cell as well as eukaryotic organelles) (Lee et al., 2006). Residues 334 and 338 in TMS8 determine the inhibitor sensitivity, protein folding and catalytic turnover (Visser et al., 2007). The porter is inhibited by nanomolar concentrations of various structurally distinct coronary vasodilator drugs, including dipyridamole, dilazep, draflazine, soluflazine and nitrobenzylmercaptopurine ribonucleoside (NBMPR) (Paproski et al., 2008).  It transports the A1 adenosine receptor agonist, tecadenoson (Lepist et al. 2013) and mediates gemcitabine (GEM) and folfirinox uptake, chemotheraputic agents for patients with metastatic pancreatic cancer (Orlandi et al. 2016).  The matricellular protein, cysteine-rich angiogenic inducer 61 (CYR61), negatively regulates synthesis of the nucleoside transporters hENT1 and hCNT3, both of which transport gemcitabine (Hesler et al. 2016). These two transporters as well as ENT2 (TC# 2.A.57.1.8) are able to take up the adenosine analogue, fludarabine (AraFA), used to treat cancer (lymphomas and leukemia) (Gorzkiewicz et al. 2018). NEM modification of Cys(416), which is located at the inner extremity of TM10, results in inhibition of hENT1 uridine transport and NBMPR binding by constraining the protein in its inward-facing conformation (Yao et al. 2018).