title: Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38.
abstract: Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure-activity relationships of reported small-molecule thiazoloquinolinones and show that several 4-cyclohexylamino analogues have potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine analogues could be acylated and functionalized with alkyne and fluorescein groups. Fluorescein analogue21bound selectively to CD38 overexpressing cells, demonstrating the potential utility of thiazoloquinolinones as small-molecule conjugates for the delivery of therapeutic and imaging agents.
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Scully
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Minden
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Ratul
authors.initials: R
authors.lastname: Mukerji
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Andrianova
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: James
authors.initials: J
authors.lastname: Kaberna
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Lentini
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Carlos
authors.initials: C
authors.lastname: Tassa
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Low
authors.affiliation: BIND Therapeutics , 325 Vassar Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: McDonnell
keywords: CD38; oncology; quinolinones; small-molecule conjugates; targeting