Evidence map›Paper›PMID 42446544›Full record

ArticleMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents2026

Discovery of pyrrolo[2,3-d]pyrimidine derivatives with inhibitory effect on liver cancer stem cell.

Xuecong Zhang, Xuechun Chen, Liwei Wang, Yiyuan Chang, Jiaxin Li, Jijian Yang, Dongxuan Ni, Ruihan Zhang, Rong Liu, Weilie Xiao

Abstract read
PubMed Publisher
In one paragraph

Article in Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Xuecong Zhang *Key Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China.
Xuechun Chen *Translational Cancer Research Center, Peking University First Hospital, Beijing, China.
Liwei WangKey Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China.
Yiyuan ChangInternational Cancer Institute, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Jiaxin LiTranslational Cancer Research Center, Peking University First Hospital, Beijing, China.
Jijian YangKey Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China.
Dongxuan NiKey Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China.
Ruihan ZhangKey Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China. zhangruihan@ynu.edu.cn.
Rong LiuTranslational Cancer Research Center, Peking University First Hospital, Beijing, China. liurong@bjmu.edu.cn.
Weilie XiaoKey Laboratory of Medicinal Chemistry for Natural Resource of Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Research & Development Center for Natural Products, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, 650500, Kunming, China. xiaoweilie@ynu.edu.cn.

Funding

Applied Basic Research Foundation of Yunnan Province 202301AW070003Applied Basic Research Foundation of Yunnan Province 202501BC070005National Natural Science Foundation of China 82073270National Natural Science Foundation of China 82260694National Natural Science Foundation of China U24A20805Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform 2022YKZY001
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. The malignancy of HCC is closely linked to liver cancer stem cells (CSCs), making the application of anti-CSC drugs a promising therapeutic approach. In this study, we report the discovery of novel pyrrolo[2,3-d]pyrimidine derivatives as potent inhibitors of liver CSC. Structural optimization and anti-CSC screening led to the identification of improved compounds 6i, 6j, and 7e, which significantly inhibited Huh7 sphere formation while exhibiting low toxicity to standard 2D-cultured tumor cells. Notably, compound 6i sensitizes both parental and Lenvatinib-resistant HCC cells to Lenvatinib treatment, showing a synergistic interaction. Collectively, these findings establish the pyrrolo[2,3-d]pyrimidine as a promising scaffold for targeting liver CSC and provide a potential combination strategy to overcome Lenvatinib resistance in advanced HCC.

Indexed as

Antineoplastic AgentsCarcinoma, HepatocellularDrug DiscoveryLiver NeoplasmsNeoplastic Stem CellsPyrimidinesPyrrolesCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureQuinolinesStructure-Activity RelationshipAntineoplastic AgentsPyrimidinesPyrrolesPyrrolo(2,3-d)pyrimidineQuinolinesCombination therapyHepatocellular carcinomaLiver cancer stem cellsPyrrolo[2,3-d]pyrimidine derivatives

Identifiers

PMID42446544

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.