title: Diversity-Oriented Synthesis for Novel, Selective and Drug-like Inhibitors for a Phosphatase from Mycobacterium Tuberculosis.
abstract: Mycobacteriumprotein tyrosine phosphatase B (mPTPB) is a potential drug target of Tuberculosis (TB). Small molecule inhibitors of mPTPB could be a treatment to overcome emerging TB drug resistance. Using a Diversity-Oriented Synthesis (DOS) strategy, we successfully developed a salicylic acid based and drug-like mPTPB inhibitor with an IC50of 2 μM and >20-fold specificity over many human PTPs, making it an excellent lead molecule for anti-TB drug discovery. In addition, DOS generated bicyclic salicylic acids are also promising starting points for acquiring inhibitors targeting other PTPs.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Rongjun
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Andrea Michelle
authors.initials: AM
authors.lastname: Gunawan
authors.affiliation: Department of Biochemistry and Molecular Biology, Chemical Genomics Core Facility, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, USA, 46202.
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang