Evidence map›Paper›PMID 39563795›Full record

ArticleACS medicinal chemistry letters2024

Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.

Daniel Lee, Ling Niu, Shilei Ding, Huile Zhu, William D Tolbert, Halima Medjahed, Guillaume Beaudoin-Bussières, Cameron Abrams, Andrés Finzi, Marzena Pazgier and 1 more

Abstract read
In one paragraph

Article in ACS 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

11 authors.

Daniel LeeDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Ling NiuInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, United States.
Shilei DingCentre de Recherche du CHUM, Montréal, Quebec H2X 0A9, Canada.
Huile ZhuDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
William D TolbertInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, United States.
Halima MedjahedCentre de Recherche du CHUM, Montréal, Quebec H2X 0A9, Canada.
Guillaume Beaudoin-BussièresCentre de Recherche du CHUM, Montréal, Quebec H2X 0A9, Canada.
Cameron AbramsDepartment of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania 19104, United States.ORCID https://orcid.org/0000-0002-1240-0816
Andrés FinziCentre de Recherche du CHUM, Montréal, Quebec H2X 0A9, Canada.
Marzena PazgierInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, United States.
Amos B SmithDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID https://orcid.org/0000-0002-1712-8567

Funding

ERASE HIV: Enterprise for Research and Advancements to Stop and Eradicate HIVUM1AI164562 · NIAID · EMORY UNIVERSITY · PI Deanna A Kulpa, Mirko Paiardini · 2021 to 2026
$30.0M
Structure-Function Analytics CoreP01AI162242 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2021 to 2025
$22.2M
Exploring HIV-1 Env open conformations for therapeutic interventionR01AI150322 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Andres Finzi, James B Munro · 2020 to 2026
$4.2M
Identifying vulnerabilities in the long-lived HIV reservoir to accelerate its decayR01AI176531 · NIAID · FRED HUTCHINSON CANCER CENTER · PI Nicolas Chomont, ANN C DUERR · 2023 to 2026
$4.1M
Assessing ADCC and Fc-mediated Protection against HIVR01AI148379 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T, FINZI, ANDRES · 2019 to 2023
$3.8M
A new strategy to eliminate HIV-1-infected cells by unlocking the Env trimerR01AI174908 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Marzena Elzbieta Pazgier · 2023 to 2026
$2.8M
NIAID NIH HHS P01 AI162242NIAID NIH HHS R01 AI148379NIAID NIH HHS R01 AI150322NIAID NIH HHS R01 AI174908NIAID NIH HHS R01 AI176531NIAID NIH HHS UM1 AI164562
6 · The paper itself

Abstract

The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 protects infected cells from antibody-dependent cellular cytotoxicity (ADCC) by limiting the exposure of vulnerable epitopes to envelope glycoprotein (Env). Small-molecule CD4 mimetics (CD4mcs) based on piperidine scaffolds represent a new family of agents capable of sensitizing HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes on Env that are recognized by non-neutralizing antibodies which are abundant in plasma of people living with HIV. Here, we employed the combined methods of parallel synthesis, structure-based design, and optimization to generate a new line of piperidine-based CD4mcs, which sensitize HIV-1 infected cells to ADCC activity. The X-ray crystallographic study of the CD4mcs within the gp120 residues suggests that the positioning of the CD4mc inside the Phe43 cavity and synergistic contact of the CD4mc with the β

Identifiers

PMID39563795
PMCPMC11571091

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.