Nolatrexed dihydrochloride

Nolatrexed dihydrochloride (AG 337) is an orally active and non-competitive lipophilic inhibitor of thymidylate synthase with a K_i of 11 nM for human thymidylate synthase. Nolatrexed dihydrochloride interacts at the folate cofactor binding site of the enzyme. Nolatrexed dihydrochloride increases sulfotransferases. Nolatrexed dihydrochloride induces cell cycle arrest in S phase of cancer cells. Nolatrexed dihydrochloride exhibits anticancer activity against cervical cancer. IC50 & Target:Ki: 11 nM (Human Thymidylate Synthase)^[1] In Vitro:Nolatrexed (6-h exposure) dihydrochloride shows a certain inhibitory effect on CCRF-CEM cells in intermittent exposure^[2].
Nolatrexed (1  nM-1.2  mM, 10 days) dihydrochloride significantly increases sulfotransferases expressions in HepG2 cells^[3].
In Vivo:Nolatrexed (1-100 mg/kg, p.o., 2 weeks) dihydrochloride significantly increases sulfotransferases expressions in rat^[3].
Nolatrexed dihydrochloride (50 mg/kg, i.v.) shows half-life, AUC, distribution factor and plasma clearance (CL) of 3.020 h, 89.972 mg/L/h, 0.831 L/kg, and 0.556 L/h/kg, respectively, in mice^[4].
Nolatrexed dihydrochloride (200 mg/kg, p.o.) shows half-life, AUC, peak time (T(max)) and peak concentration (C(max)) for orally administered drug of 5.046 h, 84.893 mg/L/h, 1.000 h, and 18.0 mg/L, respectively, in mice^[4].
Nolatrexed dihydrochloride (60 mg/m²; i.p.; every 4 h; 5 d) results in significant tumor growth retardation in nude mice bearing the HeLa Bu25TK^- human cervical cell line^[5].