生物活性

• 描述DMXAA is a competitive inhibitor of DT-diaphorase with an IC50 value of 62.5μM and a K_i value of 20μM. DMXAA blocked DT-diaphorase activity in DLD-1 cells with an IC50 value of 49.6μM. It led to approximate 25% inhibition of cytochrome b5 reductase, although the inhibition plateau was between 250μM and 2 mM^[1]. DMXAA also showed potent inhibitory effect on vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, as well as other protein kinases including homeodomain-interacting protein kinase 2, casein kinase 2, Haspin, Aurora kinases, PIM kinases, c-FMS, and tropomyosin-receptor kinases. The IC50 values of DMXAA against VEGFR1 and VEGFR2 were 119 and 11μM, respectively. DMXAA at 25μM showed partial anti-angiogenic effect in an embryonic zebrafish model. DMXAA at the concentration of 30μM significantly reduce the VEGF-induced activation of extracellular-signal-regulated kinase in human umbilical vein endothelial cells^[2]. In female Wistar rats, a single dose of DMXAA (300mg/kg, i.p.) significantly delayed the growth of NMU-induced primary mammary tumors as compared to vehicle-treated group^[3].

• 动物研究
  剂量	Mice: 17.5 mg/kg, 20 mg/kg[3] (i.p.); 30 mg/kg[4] (p.o.) Rat: 100 mg/kg - 350 mg/kg[5] (i.p.)
  给药途径	i.p., p.o.
  动物药代数据	Animal Mice[4] Dose 30 mg/kg (p.o.) 25 mg/kg (i.p. or i.v.) Administration p.o. i.p. or i.v. Cmax 358 ± 25 μmol/l (p.o.) 570 ± 21 μmol/l (i.p.) 470 ± 12 μmol/l (i.v.) T1/2 9.2 h (p.o.) 2.7 h (i.p.) 3.3 h (i.v.) AUC 1392 μmol·h/l (p.o.) 1715 μmol·h/l (i.p.) 1595 μmol·h/l (i.v.)