scholarly journals Small Molecule Inhibition of the Na+/H+ Exchange Regulatory Factor 1 and Parathyroid Hormone 1 Receptor Interaction

Biochemistry ◽  
2014 ◽  
Vol 53 (37) ◽  
pp. 5916-5922 ◽  
Author(s):  
Jeremy M. Fitzpatrick ◽  
Maria Pellegrini ◽  
Patrick R. Cushing ◽  
Dale F. Mierke
Keyword(s):  
Parathyroid Hormone ◽  
Small Molecule ◽  
Receptor Interaction ◽  
Regulatory Factor ◽  
Small Molecule Inhibition ◽  
Parathyroid Hormone 1 Receptor

Na+/H+ exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling

Nature ◽  
2002 ◽  
Vol 417 (6891) ◽  
pp. 858-861 ◽  
Author(s):  
Matthew J. Mahon ◽  
Mark Donowitz ◽  
C. Chris Yun ◽  
Gino V. Segre
Keyword(s):  
Parathyroid Hormone ◽  
Regulatory Factor ◽  
Receptor Signalling ◽  
Parathyroid Hormone 1 Receptor

Defining CBX7-Dependent Chromatin Architecture with Rapid Small-Molecule Inhibition

2019 ◽  
Author(s):  
Benjamin Z. Stanton ◽  
Binbin Lai ◽  
Gang Ren ◽  
Gangqing Hu ◽  
Kelsey N. Lamb ◽  
...  
Keyword(s):  
Small Molecule ◽  
Chromatin Architecture ◽  
Small Molecule Inhibition

scholarly journals Actions of the Small Molecule Ligands SW106 and AH-3960 on the Type-1 Parathyroid Hormone Receptor

2015 ◽  
Vol 29 (2) ◽  
pp. 307-321 ◽  
Author(s):  
Percy H. Carter ◽  
Thomas Dean ◽  
Brijesh Bhayana ◽  
Ashok Khatri ◽  
Raj Rajur ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Small Molecule ◽  
Hormone Receptor ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Blood Calcium ◽  
Parathyroid Hormone Receptor ◽  
Peptide Analog ◽  
Amino Terminal ◽  
Small Molecule Ligands

Abstract The parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating blood calcium levels and bone metabolism and is thus of interest for small-molecule ligand development. Of the few small-molecule ligands reported for the PTHR1, most are of low affinity, and none has a well-defined mechanism of action. Here, we show that SW106 and AH-3960, compounds previously identified to act as an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT, a PTHR1 construct that lacks the large amino-terminal extracellular domain used for binding endogenous PTH peptide ligands, with the same micromolar affinity with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP signaling induced by the peptide analog, M-PTH(1–11), as well as by the native PTH(1–9) sequence, as tethered to the extracellular end of transmembrane domain (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to within an extracellularly exposed area that is occupied by the N-terminal residues of PTH peptides. Additionally, they suggest that the inhibitory effects of SW106 are limited to the extracellular portions of the TMD region that mediate interactions with agonist ligands but do not extend to receptor-activation determinants situated more deeply in the helical bundle. The study helps to elucidate potential mechanisms of small-molecule binding at the PTHR1.

scholarly journals Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation

2017 ◽  
Vol 95 ◽  
pp. 94-99 ◽  
Author(s):  
Yu Yang ◽  
Yuxin Gu ◽  
Bin Wan ◽  
Xiaomin Ren ◽  
Liang-Hong Guo
Keyword(s):  
Small Molecule ◽  
Label Free ◽  
Small Molecule Inhibition ◽  
Electrochemical Biosensing
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