Evidence map›Paper›PMID 42305200›Full record

ArticleACS medicinal chemistry letters2026

Discovery of Small-Molecule GLP‑1 Receptor Agonists with Improved Oral Pharmacokinetics Based on Orforglipron.

Mengya Li, Jiahui Fang, Gaoguo Qi, Shimeng Guo, Tifei Xu, Yujie Lu, Qianting Yuan, Jiantao Wang, Simei Zhu, Jianhua Shen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2026. 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. Review
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

13 authors.

Mengya LiSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China.
Jiahui FangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Gaoguo QiSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China.
Shimeng GuoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Tifei XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yujie LuSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China.
Qianting YuanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Jiantao WangJiangsu Deyuan Pharmaceutical Co., Ltd., 29 Changjiang Road, Economic and Technological Development Zone, Lianyungang 222047, China.
Simei ZhuJiangsu Deyuan Pharmaceutical Co., Ltd., 29 Changjiang Road, Economic and Technological Development Zone, Lianyungang 222047, China.
Jianhua ShenSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China.ORCID https://orcid.org/0000-0002-9273-3409
Hanyue YangJiangsu Deyuan Pharmaceutical Co., Ltd., 29 Changjiang Road, Economic and Technological Development Zone, Lianyungang 222047, China.
Xin XieState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Kai WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID https://orcid.org/0000-0002-7597-549X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orforglipron is a leading oral small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonist for metabolic diseases; however, its oral exposure plateaus at higher doses, potentially limiting therapeutic efficacy. The solvent-exposed 4-fluoro-1-methylindazole branch of orforglipron was identified as a site amenable to modification for improving the physicochemical and pharmacokinetic properties. Systematic structure-activity relationship studies demonstrated that this region is highly tolerant of ring closure and expansion, yielding compounds

Indexed as

Food-intake-suppressingGLP-1 receptor agonistGlucose-loweringOral pharmacokineticsStructure−activity relationship

Identifiers

PMID42305200
PMCPMC13266644

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.