title: A strategy for combating melanoma with oncogenic c-Myc inhibitors and targeted nanotherapy.
abstract: OBJECTIVE
  The activity of the transcription factor c-Myc is dependent upon heterodimerization with Max to control target gene transcription. Small-molecule inhibitors of c-Myc-Max have exhibited low potency and poor water solubility and are therefore unsuitable for in vivo application. We hypothesized that a nanomedicine approach incorporating a cryptic c-Myc inhibitor prodrug could be delivered and enzymatically released in order to effectively inhibit melanoma.
  
  
  METHODS
  An Sn-2 lipase-labile Myc inhibitor prodrug was synthesized and included in two αvβ3-targeted nanoparticle platforms (20 and 200 nm). The inherent antiproliferate potency was compared with the lipid-free compound using human and mouse melanoma cell lines.
  
  
  CONCLUSIONS
  These data demonstrate for the first time a successful nanodelivery of c-Myc inhibitors and their potential use to prevent melanoma.
authors.affiliation: Department of Medicine, Washington University School of Medicine, 4320 Forest Park Avenue, Saint Louis, MO 63108, USA.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kim
authors.forename: Grace
authors.initials: G
authors.lastname: Hu
authors.forename: Deepti Sood
authors.initials: DS
authors.lastname: Gupta
authors.forename: Angana
authors.initials: A
authors.lastname: Senpan
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.forename: Anne
authors.initials: A
authors.lastname: Schmieder
authors.forename: Corban
authors.initials: C
authors.lastname: Swain
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tomasson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008545:Melanoma; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D011355:Prodrugs / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C524814:5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one; D011355:Prodrugs; D016271:Proto-Oncogene Proteins c-myc; D013844:Thiazoles
keywords: c-Myc inhibitor; melanoma; nanotherapy; prodrug