Trimelamol

Trimelamol (CB10-375; NSC283162) is a highly efficient acid-catalyzed DNA interstrand crosslinker with low neurotoxicity due to its limited BBB penetration. Trimelamol exhibits anti-tumor activity and overcomes platinum resistance. Trimelamol is investigated for lung and ovarian cancer research^{[1][2][3][4][5]}. In Vitro:

Trimelamol exerts its cytotoxicity directly through its N-hydroxymethyl group, and the toxicity is irreversible after the drug is removed. It has a faster onset of action than HMM and PMM^[1][2].

Trimelamol (0.5-500 μM, 1 h) cross-linking is its main anti-tumor mechanism. In ³²P-end-labelled pBR322 plasmid DNA, it significantly cross-links DNA at concentrations ≥ 2.5 μM, and the cross-linking efficiency is higher under acidic conditions^[3].

Trimelamol has a broad spectrum of cytotoxicity and is effective against platinum-resistant ovarian cancer cells (IC₅₀ range: 8.5-55.4 μM)^[4].

Trimelamol (15-60 mg/kg, i.p., once a day for 5 days, 4 consecutive weeks) is effective against platinum-sensitive/resistant ovarian cancer and hormone-dependent breast cancer in xenograft model mice, especially in the acquired resistance model^[4].

Trimelamol (7.5-60 mg/kg, i.p, once a day for 5 days, 3 consecutive weeks) administered parenterally was significantly effective in BALB/c female mice bearing subcutaneous T-61/MX-1 tumors and less active in BALB/c female mice bearing subcutaneous Br-10 tumors. It exhibited moderate toxicity at high doses, but manageable toxicity at low concentrations^[5].