Evidence map›Paper›PMID 36313155›Full record

ArticleACS central science2022

Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform.

Junxing Zhao, Zhichao Tang, Manikandan Selvaraju, Kristen A Johnson, Justin T Douglas, Philip F Gao, H Michael Petrassi, Michael Zhuo Wang, Jingxin Wang

Open access · diamondAbstract read
In one paragraph

Article in ACS central science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Structural Evaluations of a Selective Human STINGACS medicinal chemistry letters · 2024
    Article
  7. Review
  8. 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

9 authors at 2 institutions in 1 country.

Junxing ZhaoDepartment of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Zhichao TangDepartment of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Manikandan SelvarajuDepartment of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Kristen A JohnsonCalibr, Scripps Research Institute, La Jolla, California 92037, United States.
Justin T DouglasNuclear Magnetic Resonance Laboratory, University of Kansas, Lawrence, Kansas 66047, United States.
Philip F GaoProtein Production Group, University of Kansas, Lawrence, Kansas 66047, United States.
H Michael PetrassiCalibr, Scripps Research Institute, La Jolla, California 92037, United States.
Michael Zhuo WangDepartment of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.ORCID https://orcid.org/0000-0003-2494-4172
Jingxin WangDepartment of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.ORCID https://orcid.org/0000-0002-9414-4093
University of Kansas · USScripps Research Institute · US

Funding

Understanding the mechanobiology of stem cells in a microengineered 3D cardiac tissue environment with cardiomyopathyP20GM103638 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI HOLMSTROM, ERIK D · 2012 to 2021
$22.1M
Synthetic Chemical Biology CoreP30GM145499 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI Susan M Lunte · 2022 to 2026
$6.9M
Modulating gene expression by RNA-targeting chimerasR35GM147498 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI Jingxin Wang · 2022 to 2026
$2.1M
NIGMS NIH HHS P20 GM103638NIGMS NIH HHS P30 GM145499NIGMS NIH HHS R35 GM147498
6 · The paper itself

Abstract

Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. We tested this platform on BDW568, a newly discovered type-I interferon signaling activator, and identified stimulator of interferon genes (STING) as its target and carboxylesterase 1 (CES1) to be a key metabolizing enzyme required to activate BDW568 for target engagement. The platform we present here can be a general method applicable for target identification for a wide range of small molecules that activate different signaling pathways.

Identifiers

PMID36313155
PMCPMC9615120
OpenAlexW4296654240

What OpenQuestion 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 OpenQuestion graph.