title: First Demonstration of Positive Allosteric-like Modulation at the Human Wild Type Translocator Protein (TSPO).
abstract: We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a synthetic TSPO ligand. To the best of our knowledge this is the first demonstration of allosteric-like interaction at the wild type human TSPO.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Narlawar
authors.forename: Eryn L
authors.initials: EL
authors.lastname: Werry
authors.forename: Alana M
authors.initials: AM
authors.lastname: Scarf
authors.forename: Raphy
authors.initials: R
authors.lastname: Hanani
authors.affiliation: Dementia Research Unit, School of Medical Sciences, University of New South Wales , Sydney, NSW 2052, Australia.
authors.forename: Sook Wern
authors.initials: SW
authors.lastname: Chua
authors.forename: Victoria A
authors.initials: VA
authors.lastname: King
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Barron
authors.affiliation: School of Medical Sciences, Edith Cowan University , Joondalup, WA 6027, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Dementia Research Unit, School of Medical Sciences, University of New South Wales , Sydney, NSW 2052, Australia.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
authors.forename: Louis M
authors.initials: LM
authors.lastname: Rendina
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D000494:Allosteric Regulation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human