title: Dilazep analogues for the study of equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2).
abstract: As ENT inhibitors including dilazep have shown efficacy improving oHSV1 targeted oncolytic cancer therapy, a series of dilazep analogues was synthesized and biologically evaluated to examine both ENT1 and ENT2 inhibition. The central diamine core, alkyl chains, ester linkage and substituents on the phenyl ring were all varied. Compounds were screened against ENT1 and ENT2 using a radio-ligand cell-based assay. Dilazep and analogues with minor structural changes are potent and selective ENT1 inhibitors. No selective ENT2 inhibitors were found, although some analogues were more potent against ENT2 than the parent dilazep.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Ste 327 Johnson, 847, Monroe, Memphis, TN 38163, USA.
authors.forename: Hilaire
authors.initials: H
authors.lastname: Playa
authors.affiliation: Center for the Science of Therapeutics, The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Lewis
authors.affiliation: Center for the Science of Therapeutics, The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Amal
authors.initials: A
authors.lastname: Ting
authors.affiliation: Center for the Science of Therapeutics, The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Suh
authors.affiliation: Center for the Science of Therapeutics, The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Benito
authors.initials: B
authors.lastname: Muñoz
authors.affiliation: Neurosurgery Department, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Matuza
authors.affiliation: Neurosurgery Department, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Passer
authors.affiliation: Center for the Science of Therapeutics, The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Ste 327 Johnson, 847, Monroe, Memphis, TN 38163, USA. Electronic address: john.buolamwini@rosalindfranklin.edu.
authors.forename: John K
authors.initials: JK
authors.lastname: Buolamwini
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004109:Dilazep / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D033721:Equilibrative Nucleoside Transporter 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D033722:Equilibrative-Nucleoside Transporter 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013552:Swine
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D011994:Recombinant Proteins; D004109:Dilazep
keywords: Dilazep; Equilibrative nucleoside transporters (ENTs); hENT1; hENT2; rENT2