Evidence map›Paper›PMID 37974942›Full record

ArticleACS medicinal chemistry letters2023

Lipid Tales: Optimizing Arylomycin Membrane Anchors.

Michael F T Koehler, Yi-Chen Chen, Yongsheng Chen, Yuan Chen, James J Crawford, Matthew R Durk, Keira Garland, Emily J Hanan, Robert I Higuchi, Huiyong Hu and 7 more

Open access · greenAbstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

17 authors at 1 institution in 1 country.

Michael F T KoehlerDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.ORCID https://orcid.org/0000-0003-0967-8304
Yi-Chen ChenDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California 94080, United States.
Yongsheng ChenDepartment of Chemistry, WuXi AppTec, Shanghai 200131, China.
Yuan ChenDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California 94080, United States.
James J CrawfordDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.ORCID https://orcid.org/0000-0002-6408-8246
Matthew R DurkDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California 94080, United States.
Keira GarlandDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.
Emily J HananDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.ORCID https://orcid.org/0000-0001-7681-9424
Robert I HiguchiRQx Pharmaceuticals, La Jolla, California 92037, United States.
Huiyong HuDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.
Cuong Q LyDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.
Prasuna G ParaselliRQx Pharmaceuticals, La Jolla, California 92037, United States.
Tucker C RobertsRQx Pharmaceuticals, La Jolla, California 92037, United States.
Jacob B SchwarzDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, California 94080, United States.
Peter A SmithDepartment of Infectious Disease, Genentech, Inc., South San Francisco, California 94080, United States.
Zhiyong YuDepartment of Chemistry, WuXi AppTec, Shanghai 200131, China.
Christopher E HeiseDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
WuXi AppTec (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts, no new antibiotic class with activity against Gram-negative bacteria has been approved in over 50 years. LepB inhibitors (LepBi) based on the arylomycin class of natural products are a novel class of antibiotics and function by inhibiting the bacterial type I signal peptidase (SPase) in Gram-negative bacteria. One critical aspect of LepBi development involves optimization of the membrane-anchored lipophilic portion of the molecule. We therefore developed an approach that assesses the effect of this portion on the complicated equilibria of plasma protein binding, crossing the outer membrane of Gram-negative bacteria and anchoring in the bacterial inner membrane to facilitate SPase binding. Our findings provide important insights into the development of antibacterial agents where the target is associated with the inner membrane of Gram-negative bacteria.

Identifiers

PMID37974942
PMCPMC10641904
OpenAlexW4387526637

What OpenQuestion holds

Textmetadata
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.