title: Indirubin derivatives: a patent review (2010 - present).
abstract: BACKGROUND
  Indirubins are bisindole alkaloids naturally occurring in indigo-bearing plants or in mollusks from the Muricidae family. They belong to the rather small family of indigoids, which has nevertheless found an extreme importance in the fields of dyes and medicinal chemistry. Indirubin has been found to be the active ingredient of a traditional Chinese Medicine used to treat the symptoms of leukemia. Further biological explorations revealed the ability of indirubin to bind cyclin-dependent kinases and 6-bromoindirubin, extracted from mollusks, to bind glycogen synthase kinase-3. The high affinity displayed by the two natural products has opened a vast field of research and triggered the development of hundred of derivatives with biological activities.
  
  
  METHODS
  The traditional use of indirubin for the treatment of leukemia has prompted different research groups to study the cytotoxic effect of indirubin derivatives on both solid tumors and leukemia. Moreover, the affinity of indirubins for kinases also allowed the exploration of their activity towards stem cells.
  
  
  CONCLUSIONS
  The derivatives presented are in accordance with first discoveries and establish the close relation between activity and kinase inhibition. New derivatives have been patented and new interferences in signaling pathways are described. However, few in vivo studies have been performed and more efficient solutions are needed to unravel the major issue of solubility.
authors.affiliation: University of Athens, Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy , Panepistimiopolis Zografou, GR-15771, Athens , Greece skaltsounis@pharm.uoa.gr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaboriaud-Kolar
authors.forename: Konstantina
authors.initials: K
authors.lastname: Vougogiannopoulou
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008516:Medicine, Chinese Traditional; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010330:Patents as Topic; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C027185:indirubin
keywords: cancer; derivatives; indirubin; kinases; leukemia; patents; stem cells