title: Natural products reveal cancer cell dependence on oxysterol-binding proteins.
abstract: Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)--proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. The functions of OSBP and the ORPs, however, remain largely enigmatic. Based on our findings, we have named the aforementioned natural products ORPphilins. Here we used ORPphilins to reveal new cellular activities of OSBP. The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Anthony W G
authors.initials: AW
authors.lastname: Burgett
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Poulsen
authors.forename: Kittikhun
authors.initials: K
authors.lastname: Wangkanont
authors.forename: D Ryan
authors.initials: DR
authors.lastname: Anderson
authors.forename: Chikako
authors.initials: C
authors.lastname: Kikuchi
authors.forename: Kousei
authors.initials: K
authors.lastname: Shimada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okubo
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Fortner
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mimaki
authors.forename: Minpei
authors.initials: M
authors.lastname: Kuroda
authors.forename: Jason P
authors.initials: JP
authors.lastname: Murphy
authors.forename: David J
authors.initials: DJ
authors.lastname: Schwalb
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Petrella
authors.forename: Ivan
authors.initials: I
authors.lastname: Cornella-Taracido
authors.forename: Markus
authors.initials: M
authors.lastname: Schirle
authors.forename: John A
authors.initials: JA
authors.lastname: Tallarico
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Shair
mesh_terms: D001688:Biological Products / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002783:Cholestenones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D009369:Neoplasms / Q000378:metabolism*; D010619:Phenazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012503:Saponins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013109:Sphingomyelins / Q000096:biosynthesis; D013141:Spiro Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013256:Steroids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013267:Stilbenes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000098825:Oxysterol Binding Proteins
chemical_list: D001688:Biological Products; D002352:Carrier Proteins; D002783:Cholestenones; D006888:Hydroxycholesterols; D010619:Phenazines; D011987:Receptors, Steroid; D012503:Saponins; D013109:Sphingomyelins; D013141:Spiro Compounds; D013256:Steroids; D013267:Stilbenes; D000098825:Oxysterol Binding Proteins; C473897:ritterazine B; C117232:schweinfurthin; C454806:cephalostatin I; C106408:OSW 1; C007997:25-hydroxycholesterol