Evidence map›Paper›PMID 38815872›Full record

ArticleBioorganic & medicinal chemistry letters2024

Identification of highly potent and selective HTRA1 inhibitors.

David G Dennis, Young Joo Sun, Dylan E Parsons, Vinit B Mahajan, Mark Smith

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

5 authors.

David G DennisMedicinal Chemistry Knowledge Center, Sarafan ChEM-H, Stanford University, CA 94305, USA; Molecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, CA 94304, USA.
Young Joo SunMolecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, CA 94304, USA.
Dylan E ParsonsMedicinal Chemistry Knowledge Center, Sarafan ChEM-H, Stanford University, CA 94305, USA; Molecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, CA 94304, USA.
Vinit B MahajanMolecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, CA 94304, USA; Veterans Affairs Palo Alto Health Care System, CA 94304, USA. Electronic address: vinit.mahajan@stanford.com.
Mark SmithMedicinal Chemistry Knowledge Center, Sarafan ChEM-H, Stanford University, CA 94305, USA. Electronic address: mxsmith@stanford.edu.

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Stanford Vision Training ProgramT32EY027816 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2018 to 2026
$2.0M
NEI NIH HHS P30 EY026877NEI NIH HHS T32 EY027816
6 · The paper itself

Abstract

High temperature requirement A serine peptidase 1 (HTRA1) is a serine protease involved in an array of signaling pathways. It is also responsible for the regulation of protein aggregates via refolding, translocation, and degradation. It has subsequently been found that runaway proteolytic HTRA1 activity plays a role in a variety of diseases, including Age-Related Macular Degeneration (AMD), osteoarthritis, and Rheumatoid Arthritis. Selective inhibition of serine protease HTRA1 therefore offers a promising new strategy for the treatment of these diseases. Herein we disclose structure-activity-relationship (SAR) studies which identify key interactions responsible for binding affinity of small molecule inhibitors to HTRA1. The study results in highly potent molecules with IC

Indexed as

High-Temperature Requirement A Serine Peptidase 1Serine EndopeptidasesDose-Response Relationship, DrugHumansMolecular StructureSerine Proteinase InhibitorsSmall Molecule LibrariesStructure-Activity RelationshipHigh-Temperature Requirement A Serine Peptidase 1HTRA1 protein, humanSerine EndopeptidasesSerine Proteinase InhibitorsSmall Molecule LibrariesAge-related macular degenerationHTRA1PeptidomimeticsProtease inhibitorStructure–activity relationship studies

Identifiers

PMID38815872
PMCPMC11214877

What OpenQuestion holds

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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.