Trabectedin is a multimodal, synthetically produced antitumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. The drug exerts its activity by targeting the transcriptional machinery and impairing DNA repair. It is approved in close to 80 countries in North America, Europe, South America and Asia for the treatment of advanced soft tissue sarcomas as a single-agent and for relapsed ovarian cancer in combination with DOXIL®/CAELYX® (doxorubicin HCl liposome injection) in the European Union.
Plitidepsin (Aplidin®) is an anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. It specifically binds to the eEF1A2 and targets the non-canonical role of this protein, resulting in tumor cell death via apoptosis (programed death). Plitidepsin is approved Australia for the treatment of multiple myeloma, and it has received orphan drug designation in the European Union and the United States of America.
ZepzelcaTM (lurbinectedin), also known as PM1183, is an analog of the marine compound ET-736 isolated from the sea squirt Ecteinacidia turbinata in which a hydrogen atom has been replaced by a methoxy group. It is a selective inhibitor of the oncogenic transcription programs on which many tumors are particularly dependent. Together with its effect on cancer cells, lurbinectedin inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumor. Transcriptional addiction is an acknowledged target in those diseases, many of them lacking other actionable targets.
PM184 is a marine-derive drug found in a sponge called Lithoplocamia lithistoides. This drug candidate is a microtubule inhibitor that targets a protein called tubulin in a novel way. It blocks cancer growth by impairing cell division of tumor cells through the inhibition of a crucial process called mitosis. It is currently being investigated in a Phase II trial for hormone-receptor positive, HER2-negative locally advanced and/or metastatic breast cancer and in studies in various solid tumors and in other Phase II solid tumor trials.
Clinical studies with PM184 in clinicaltrial.gov
PM14 is a synthetic compound under clinical investigation. It is a specific inhi-bitor of oncogenic transcription, which has demonstrated encouraging pre-clinical activity in several cancer models. Many tumors are addicted to specific oncogenic transcription programs, this addiction constituting a distinctive target that can be exploited for the treatment of patients.