Cystine-knot peptides: emerging tools for cancer imaging and therapy

Expert Rev Proteomics. 2014 Oct;11(5):561-72. doi: 10.1586/14789450.2014.932251. Epub 2014 Aug 28.


Cystine-knot miniproteins, also known as knottins, constitute a large family of structurally related peptides with diverse amino acid sequences and biological functions. Knottins have emerged as attractive candidates for drug development as they potentially fill a niche between small molecules and protein biologics, offering drug-like properties and the ability to bind to clinical targets with high affinity and selectivity. Due to their extremely high stability and unique structural features, knottins also demonstrate promise in addressing challenging drug development goals, including the potential for oral delivery and the ability to access intracellular drug targets. Several naturally-occurring knottins have recently received approval for treating chronic pain and irritable bowel syndrome, while others are under development for tumor imaging applications. To expand beyond nature's repertoire, rational and combinatorial protein engineering methods are generating tumor-targeting knottins for use as cancer diagnostics and therapeutics.

Keywords: disulfide-rich peptides; drug discovery; knottin; miniprotein; molecular imaging; protein engineering; therapeutics; tumor targeting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Chronic Pain / drug therapy
  • Cyclotides / therapeutic use
  • Cystine-Knot Miniproteins / metabolism
  • Cystine-Knot Miniproteins / therapeutic use*
  • Humans
  • Irritable Bowel Syndrome / drug therapy
  • Molecular Imaging / methods
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Protein Engineering
  • Radiopharmaceuticals* / metabolism


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cyclotides
  • Cystine-Knot Miniproteins
  • Radiopharmaceuticals