Evidence map›Paper›PMID 37131728›Full record

ArticlebioRxiv : the preprint server for biology2023

A biophysical rationale for the selective inhibition of PTP1B over TCPTP by nonpolar terpenoids.

Anika J Friedman, Hannah M Padgette, Levi Kramer, Evan T Liechty, Gregory W Donovan, Jerome M Fox, Michael R Shirts

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Anika J FriedmanUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Hannah M PadgetteUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Levi KramerUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Evan T LiechtyUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Gregory W DonovanUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Jerome M FoxUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
Michael R ShirtsUniversity of Colorado Boulder Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309.
University of Colorado Boulder · US

Funding

Microbially guided discovery and biosynthesis of biologically active natural productsR35GM143089 · NIGMS · UNIVERSITY OF COLORADO · PI FOX, JEROME · 2021 to 2025
$1.8M
NIGMS NIH HHS R35 GM143089
6 · The paper itself

Abstract

Protein tyrosine phosphatases (PTPs) are emerging drug targets for many diseases, including type 2 diabetes, obesity, and cancer. However, a high degree of structural similarity between the catalytic domains of these enzymes has made the development of selective pharmacological inhibitors an enormous challenge. Our previous research uncovered two unfunctionalized terpenoid inhibitors that selectively inhibit PTP1B over TCPTP, two PTPs with high sequence conservation. Here, we use molecular modeling with experimental validation to study the molecular basis of this unusual selectivity. Molecular dynamics (MD) simulations indicate that PTP1B and TCPTP contain a conserved h-bond network that connects the active site to a distal allosteric pocket; this network stabilizes the closed conformation of the catalytically influential WPD loop, which it links to the L-11 loop and

Identifiers

PMID37131728
PMCPMC10153121
OpenAlexW4366428227

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.