Evidence map›Paper›PMID 38628802›Full record

ArticleACS medicinal chemistry letters2024

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Darryl Kato, Regina Wai-Yan Choy, Eda Canales, Ryan A Dick, April D Lake, Nathan D Shapiro, Elbert Chin, Jiayao Li, Jennifer R Zhang, Qiaoyin Wu and 12 more

Open access · greenAbstract 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, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 40% 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

1 citing paper in PubMed, 1 synthesis or guideline pooled it, 1 citations in OpenAlex.

  1. Pooled it
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

22 authors at 5 institutions in 1 country.

Darryl KatoGilead Sciences, Foster City, California 94404, United States.ORCID https://orcid.org/0009-0002-4158-7525
Regina Wai-Yan ChoyGilead Sciences, Foster City, California 94404, United States.
Eda CanalesGilead Sciences, Foster City, California 94404, United States.
Ryan A DickMaze Therapeutics, South San Francisco, California 94080, United States.
April D LakeGilead Sciences, Foster City, California 94404, United States.
Nathan D ShapiroGilead Sciences, Foster City, California 94404, United States.
Elbert ChinGilead Sciences, Foster City, California 94404, United States.
Jiayao LiGilead Sciences, Foster City, California 94404, United States.
Jennifer R ZhangGilead Sciences, Foster City, California 94404, United States.
Qiaoyin WuGilead Sciences, Foster City, California 94404, United States.
Roland D SaitoGilead Sciences, Foster City, California 94404, United States.
Sammy MetoboCircle Pharma, South San Francisco, California 94080, United States.
Evangelos AktoudianakisGilead Sciences, Foster City, California 94404, United States.
Scott D SchroederGilead Sciences, Foster City, California 94404, United States.
Zheng-Yu YangGilead Sciences, Foster City, California 94404, United States.
Dylan M Glatt23andMe Therapeutics, South San Francisco, California 94080, United States.
Scott BalsitisGilead Sciences, Foster City, California 94404, United States.
Lindsay GamelinGilead Sciences, Foster City, California 94404, United States.
Mei YuGilead Sciences, Foster City, California 94404, United States.
Guofeng ChengAusperBio Therapeutics Inc., San Mateo, California 94401, United States.
William E DelaneyAssembly Bio, South San Francisco, California 94080, United States.
John O LinkGilead Sciences, Foster City, California 94404, United States.
Gilead Sciences (United States) · USAssembly Biosciences (United States) · USIo Therapeutics (United States) · USMaze (United States) · USRapt Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure. A series of dihydropyridoisoquinolizinone (DHQ) inhibitors of human poly(A) polymerases PAPD5/7 were reported to suppress HBsAg in vitro. An example from this class, RG7834, briefly entered the clinic. We set out to identify a potent, orally bioavailable, and safe PAPD5/7 inhibitor as a potential component of a functional cure regimen. Our efforts led to the identification of a dihydropyridophthalazinone (DPP) core with improved pharmacokinetic properties. A conformational restriction strategy and optimization of core substitution led to GS-8873, which was projected to provide deep HBsAg suppression with once-daily dosing.

Identifiers

PMID38628802
PMCPMC11017420
OpenAlexW4393072071

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.