Evidence map›Paper›PMID 34820623›Full record

ReviewRSC medicinal chemistry2021

Monobodies as tool biologics for accelerating target validation and druggable site discovery.

Padma Akkapeddi, Kai Wen Teng, Shohei Koide

Open access · hybridAbstract readReview
In one paragraph

Review in RSC medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. 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

3 authors at 1 institution in 1 country.

Padma AkkapeddiPerlmutter Cancer Center, New York University Langone Medical Center New York NY USA Shohei.Koide@nyulangone.org.ORCID https://orcid.org/0000-0002-4012-9568
Kai Wen TengPerlmutter Cancer Center, New York University Langone Medical Center New York NY USA Shohei.Koide@nyulangone.org.ORCID https://orcid.org/0000-0001-6898-9642
Shohei KoidePerlmutter Cancer Center, New York University Langone Medical Center New York NY USA Shohei.Koide@nyulangone.org.ORCID https://orcid.org/0000-0001-5473-4358
NYU Langone Health · US

Funding

Probing RAS-mediated Signaling with Monobody InhibitorsR01CA212608 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHOHEI KOIDE, John P O'Bryan · 2017 to 2026
$5.8M
Molecular mechanisms of SHP2 signaling dissected with designer binding proteinsR01CA194864 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KOIDE, SHOHEI · 2016 to 2020
$1.8M
Accurate prediction of neutralization capacity from deep mining of SARS-CoV-2 serologyR21AI158997 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KOIDE, SHOHEI · 2020 to 2020
$466k
NCI NIH HHS R01 CA194864NCI NIH HHS R01 CA212608NIAID NIH HHS R21 AI158997
6 · The paper itself

Abstract

Despite increased investment and technological advancement, new drug approvals have not proportionally increased. Low drug approval rates, particularly for new targets, are linked to insufficient target validation at early stages. Thus, there remains a strong need for effective target validation techniques. Here, we review the use of synthetic binding proteins as tools for drug target validation, with focus on the monobody platform among several advanced synthetic binding protein platforms. Monobodies with high affinity and high selectivity can be rapidly developed against challenging targets, such as KRAS mutants, using protein engineering technologies. They have strong tendency to bind to functional sites and thus serve as drug-like molecules, and they can serve as targeting ligands for constructing bio-PROTACs. Genetically encoded monobodies are effective "tool biologics" for validating intracellular targets. They promote crystallization and help reveal the atomic structures of the monobody-target interface, which can inform drug design. Using case studies, we illustrate the potential of the monobody technology in accelerating target validation and small-molecule drug discovery.

Identifiers

PMID34820623
PMCPMC8597423
OpenAlexW3199780024

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.