PM-00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. PM-00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. Immunohistochemical studies in tumors also demonstrated histone-H2AX phosphorylation and p53 overexpression. PM-00104 has progressed into phase II clinical trials to treat Ewing sarcoma, urothelial carcinoma, multiple myeloma, endometrial and cervical cancer. The phase II study concluded that there were no objective responses in the cohort of 16 evaluable patients with Ewing sarcoma. The study of Urothelial carcinoma treatment was terminated early because there seemed to be no benefit from the current therapy. Moreover, PM-00104 as a single-agent did not prove to be an effective therapy for patients with advanced/metastatic endometrial or cervical cancer. None achieved objective tumor response was in phase II study for the treatment of advanced/metastatic endometrial or cervical cancer. Preliminary data showed PM-00104 to be safe to use in the treatment of multiple myeloma but the complete results from this trial have not been published.