Discovery of a 9-mer Cationic Peptide (LTX-315) as a Potential First in Class Oncolytic Peptide

作者：Haug Bengt Erik^*; Camilio Ketil Andre; Eliassen Liv Tone; Stensen Wenche; Svendsen John Sigurd; Berg Kristel; Mortensen Bjarte; Serin Guillaume; Mirjolet Jean Francois; Bichat Francis; Rekdal Oystein^*

来源：Journal of Medicinal Chemistry, 2016, 59(7): 2918-2927.

DOI：10.1021/acs.jmedchem.5b02025

Oncolytic immunotherapies represent a new promising strategy in the treatment of cancer. In our efforts to develop oncolytic peptides, we identified a series of chemically modified 9-mer cationic peptides that were highly effective against both drug-resistant and drug-sensitive cancer cells and with lower toxicity toward normal cells. Among these peptides, LTX-315 displayed superior anticancer activity and was selected as a lead candidate. This peptide showed relative high plasma protein binding abilities and a human plasma half-life of 160 min, resulting in formation of nontoxic metabolites. In addition, the lead candidate demonstrated relatively low ability to inhibit CYP450 enzymes. Collectively these data indicated as a new anticancer agent for intratumoral administration and is currently being evaluated in a phase I/IIa study.

• 出版日期2016-4-14