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

J Med Chem. 2016 Apr 14;59(7):2918-27. doi: 10.1021/acs.jmedchem.5b02025. Epub 2016 Mar 29.


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 that this peptide has potential to be developed as a new anticancer agent for intratumoral administration and is currently being evaluated in a phase I/IIa study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacology*
  • Blood Proteins
  • Cell Line, Tumor / drug effects
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology
  • Dogs
  • Drug Discovery
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Half-Life
  • Humans
  • Mice, Inbred BALB C
  • Oligopeptides / blood*
  • Oligopeptides / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Rats


  • Antineoplastic Agents
  • Blood Proteins
  • Cytochrome P-450 Enzyme Inhibitors
  • LTX-315
  • Oligopeptides
  • Peptides