Evidence map›Paper›PMID 39334953›Full record

ArticleBiomolecules2024

Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.

Jason Shirian, Alexandra Hockla, Justyna J Gleba, Matt Coban, Naama Rotenberg, Laura M Strik, Aylin Alasonyalilar Demirer, Matt L Pawlush, John A Copland, Evette S Radisky and 1 more

Abstract read
In one paragraph

Article in Biomolecules, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jason ShirianDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.ORCID 0000-0001-8380-3332
Alexandra HocklaDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
Justyna J GlebaDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
Matt CobanDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.ORCID 0000-0001-6396-6759
Naama RotenbergDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Laura M StrikDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
Aylin Alasonyalilar DemirerDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
Matt L PawlushDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.ORCID 0009-0006-4586-3389
John A CoplandDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.
Evette S RadiskyDepartment of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL 32224, USA.ORCID 0000-0003-3121-109X
Julia M ShifmanDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.ORCID 0000-0001-6678-6497

Funding

Engineering tissue inhibitor of metalloproteinases-2 (TIMP-2) for triple negative breast cancer therapyR01CA258274 · NCI · MAYO CLINIC JACKSONVILLE · PI RADISKY, EVETTE S · 2021 to 2025
$1.6M
Engineering selective inhibition of metalloproteinases by tissue inhibitors of metalloproteinases (R01 GM132100 RESUB - *TIMPs)R01GM132100 · NIGMS · MAYO CLINIC JACKSONVILLE · PI RADISKY, EVETTE S · 2020 to 2023
$1.3M
NCI NIH HHS R01 CA258274NIGMS NIH HHS R01 GM132100NIH HHS 5R01CA258274-04A1
6 · The paper itself

Abstract

Matrix metalloproteinases (MMPs) are significant drivers of many diseases, including cancer, and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous MMP inhibitors and are being pursued for the development of anti-MMP therapeutics. TIMPs possess many attractive properties for drug candidates, such as complete MMP inhibition, low toxicity, low immunogenicity, and high tissue permeability. However, a major challenge with TIMPs is their rapid clearance from the bloodstream due to their small size. This study explores a method for extending the plasma half-life of the N-terminal domain of TIMP2 (N-TIMP2) by appending it with a long, intrinsically unfolded tail containing Pro, Ala, and Thr (PATylation). We designed and produced two PATylated N-TIMP2 constructs with tail lengths of 100 and 200 amino acids (N-TIMP2-PAT

Indexed as

Matrix Metalloproteinase 9Tissue Inhibitor of Metalloproteinase-2AnimalsHalf-LifeHumansMatrix Metalloproteinase InhibitorsMicePeptidesProtein UnfoldingMatrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsPeptidesTIMP2 protein, humanTissue Inhibitor of Metalloproteinase-2half-life extensionmatrix metalloprotein inhibitorsPASylationPATylationtherapeutic proteinTIMP

Identifiers

PMID39334953
PMCPMC11429640

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.