Evidence map›Paper›PMID 35642311›Full record

ArticleArchiv der Pharmazie2022

Characterization of caspase-2 inhibitors based on specific sites of caspase-2-mediated proteolysis.

Merlin Bresinsky, Jessica M Strasser, Alexander Hubmann, Bernadette Vallaster, William M McCue, Jessica Fuller, Gurpreet Singh, Kathryn M Nelson, Matthew E Cuellar, Barry C Finzel and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archiv der Pharmazie, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 42% of its field
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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias.Translational research : the journal of laboratory and clinical medicine · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Merlin BresinskyInstitute of Pharmacy, University of Regensburg, Regensburg, Germany.
Jessica M StrasserDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Alexander HubmannInstitute of Pharmacy, University of Regensburg, Regensburg, Germany.
Bernadette VallasterInstitute of Pharmacy, University of Regensburg, Regensburg, Germany.
William M McCueDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Jessica FullerDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Gurpreet SinghDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Kathryn M NelsonDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Matthew E CuellarDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Barry C FinzelDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Karen H AsheDepartment of Neurology, University of Minnesota, Minneapolis, Minnesota, USA.
Michael A WaltersDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Steffen PockesInstitute of Pharmacy, University of Regensburg, Regensburg, Germany.ORCID http://orcid.org/0000-0002-2211-9868
University of Minnesota · USUniversity of Regensburg · DE

Funding

Caspase-2 Probe CompoundsR01AG062199 · NIA · UNIVERSITY OF MINNESOTA · PI ASHE, KAREN H, WALTERS, MICHAEL A. · 2019 to 2023
$3.9M
Deutsche Forschungsgemeinschaft Forschungsstipendium 436921318Fonds der Chemischen Industrie SK-208/16Lucas Brothers FoundationNIA NIH HHS R01 AG062199NIH HHS R01-AG62199
6 · The paper itself

Abstract

Since the discovery of the caspase-2 (Casp2)-mediated ∆tau314 cleavage product and its associated impact on tauopathies such as Alzheimer's disease, the design of selective Casp2 inhibitors has become a focus in medicinal chemistry research. In the search for new lead structures with respect to Casp2 selectivity and drug-likeness, we have taken an approach by looking more closely at the specific sites of Casp2-mediated proteolysis. Using seven selected protein cleavage sequences, we synthesized a peptide series of 53 novel molecules and studied them using in vitro pharmacology, molecular modeling, and crystallography. Regarding Casp2 selectivity, AcITV(Dab)D-CHO (23) and AcITV(Dap)D-CHO (26) demonstrated the best selectivity (1-6-fold), although these trends were only moderate. However, some analogous tetrapeptides, most notably AcDKVD-CHO (45), showed significantly increased Casp3 selectivities (>100-fold). Tetra- and tripeptides display decreased or no Casp2 affinity, supporting the assumption that a motif of five amino acids is required for efficient Casp2 inhibition. Overall, the results provide a reasonable basis for the development of both selective Casp2 and Casp3 inhibitors.

Indexed as

Caspase 2Caspase 3Caspase InhibitorsProteolysisStructure-Activity RelationshipCaspase 2Caspase 3Caspase InhibitorsAlzheimer's diseasecaspase-2caspase-2 inhibitorsprotein cleavagetauopathies

Identifiers

PMID35642311
PMCPMC9616052
OpenAlexW4281755334

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.