Disease relevance of NSC 283162

• Phase II trial of trimelamol in refractory ovarian cancer [1].
• BRL 43694 also substantially reduced the vomiting induced by cyclophosphamide:doxorubicin, and prevented the trimelamol-induced emesis [2].
• It is likely that this reduction in toxicity may be explained by the relatively poor ability of Trimelamol to enter the CNS [3].
• Trimelamol had similar activity to PMM against the murine PC6 plasmacytoma, but enhanced activity with respect to PMM against the Walker 256 carcinosarcoma in the rat, a species which metabolizes PMM less efficiently [4].

High impact information on NSC 283162

• Phase I trial and pharmacokinetics of trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine) [5].
• Trimelamol gave rise to DNA-interstrand crosslinks in naked plasmid DNA and in cultured cell lines, whereas the analogues failed to do so under a variety of experimental conditions [6].
• Stable analogues of the antitumour agent trimelamol retain in vitro cytotoxicity in drug-sensitive and resistant rodent and human cell lines [7].
• An investigation of the mechanism of action of the antitumour agent trimelamol has established that it is an efficient interstrand DNA cross-linker in vitro, comparable to nitrogen mustards such as melphalan [8].
• This difference did not correlate with plasma protein binding which is greater for PMM (68.2%) than for Trimelamol (17.5%) [3].

Chemical compound and disease context of NSC 283162

• Superior efficacy of trimelamol to hexamethylmelamine in human ovarian cancer xenografts [9].

Biological context of NSC 283162

• Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature [10].

Associations of NSC 283162 with other chemical compounds

• Preclinical toxicology, pharmacokinetics and formulation of N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine (trimelamol), a water-soluble cytotoxic s-triazine which does not require metabolic activation [4].

Gene context of NSC 283162

• In vivo studies using a human ovarian cancer xenograft model PXN/65 showed TM to be curative in the dose range of 15-60 mg/kg i.p. daily x 5, for 4 weeks [11].

Analytical, diagnostic and therapeutic context of NSC 283162

• An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products [10].
• The prototype containing 30 mg/mL trimelamol in a 50% PEG 3400-aqueous vehicle was found to be the optimal formulation for sterile filtration, lyophilization, and subsequent reconstitution [12].

References