TMZ(Temozolomide)

194, 15

DBA/2 mice with L-1210 and L-1210/BCNU cells

Methazolastone plus TPI 287 has entered in a phase II clinical trial in the treatment of melanoma.

40 mg/kg

Methazolastone causes formation of DNA alkali-labile sites which are present in similar amounts and repaired at a similar rate in L-1210 and L-1210/BCNU. In L-1210 but not in L-1210/BCNU methazolastone induces an arrest of cells in SL-G2-M phases. Methazolastone induces a similar amount of DNA ALS which is also repaired at a similar rate in L-1210 and L-1210/BCNU cell lines. Methazolastone induces a similar amount of DNA ALS which is also repaired at a similar rate in L-1210 and L-1210/BCNU cell lines. [1] Methazolastone sensitivity of both chemo-sensitive and resistant cells (D54-R and U87-R) is enhanced significantly under hyperoxia. Both Methazolastone and hyperoxia are associated with increased phosphorylation of ERK p44/42 MAPK (Erk1/2), but to a lesser extent in D54-R cells, suggesting that Erk1/2 activity may be involved in regulation of hyperoxia and Methazolastone-mediated cell death. Hyperoxia enhances Methazolastone toxicity in GBM cells by induction of apoptosis, possibly via MAPK-related pathways. [2] Methazolastone induces in monocytes the DNA damage response pathways ATM-Chk2 and ATR-Chk1 resulting in p53 activation. [3] Chronic Methazolastone exposure results in acquired Methazolastone-resistance and elevates miR-21 expression. [4] Methazolastone treatment triggers endoplasmic reticula (ER) stress with increased expression of GADD153 and GRP78 proteins, and deceases pro-caspase 12 protein. Methazolastone induces autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. [5]

l hours

DMSO 39 mg/mL, Water 5 mg/mL, Ethanol <1 mg/mL

Methazolastone is a second-generation alkylating agent.