Evidence map›Paper›PMID 40044142›Full record

ArticleJournal of medicinal chemistry2025

2FA-Platform Generates Dual Fatty Acid-Conjugated GLP-1 Receptor Agonist TE-8105 with Enhanced Diabetes, Obesity, and NASH Efficacy Compared to Semaglutide.

Mun-Teng Wong, Pei-Hsuan Lin, Wei-Chen Lin, Chi-Jiun Peng, Jon D Wright, Hui-Ju Lee, Hsing-Mao Chu, Carmay Lim, Tse Wen Chang

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. 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.

Mun-Teng WongImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.ORCID 0009-0004-8505-4530
Pei-Hsuan LinImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.
Wei-Chen LinT-E Meds, Inc., C423, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.
Chi-Jiun PengT-E Meds, Inc., C423, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.
Jon D WrightImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.ORCID 0000-0002-2378-7649
Hui-Ju LeeT-E Meds, Inc., C423, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.
Hsing-Mao ChuImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.
Carmay LimImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.ORCID 0000-0001-9077-7769
Tse Wen ChangImmunwork, Inc., C520, No. 99, Lane 130, Academia Road, Section 1, Nangang, Taipei 115021, Taiwan.ORCID 0000-0002-8761-3760

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Conjugating two fatty acids (2FAs) to peptide drugs can improve pharmacokinetics and therapeutic effects. However, optimizing FA spacing, chain combination, and attachment site to simultaneously enhance albumin binding and drug efficacy remains challenging. We introduce a multiarm linker technology enabling precise control of 2FA spacing, composition, and attachment. By applying this technology to a modified glucagon-like peptide-1 (GLP-1) and screening various 2FA-GLP-1 conjugates differing in linkage, linker, and FA properties for improved albumin affinity, pharmacokinetics, and pharmacodynamics, TE-8105 emerged as a promising candidate. TE-8105 outperformed semaglutide, showing improved long-term glycemic control, weight loss, and liver health in diabetic mice, and dose-dependent weight loss and favorable body composition changes in obese mice. A distinct advantage of TE-8105 over semaglutide is its low-dose reduction of liver steatosis and improvement of liver health in nonalcoholic steatohepatitis mice. The multiarm linker technology provides a versatile platform for developing improved 2FA-peptide therapeutics.

Indexed as

Fatty AcidsGlucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesNon-alcoholic Fatty Liver DiseaseObesityAnimalsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Glucagon-Like Peptide 1HumansHypoglycemic AgentsMaleMiceMice, Inbred C57BLSemaglutideFatty AcidsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesHypoglycemic AgentsSemaglutide

Identifiers

PMID40044142
PMCPMC11956005

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.