Evidence map›Paper›PMID 38100041›Full record

ArticleJournal of medicinal chemistry2023

Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.

Wenchao Wang, Xiang Ling, Ruojiong Wang, Haonan Xiong, Liuzhi Hu, Zhikun Yang, Hong Wang, Yali Zhang, Wenjie Wu, Prashant K Singh and 3 more

Open access · greenAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2023. 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
1.1field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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 at 3 institutions in 2 countries.

Wenchao WangCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.ORCID 0000-0003-0757-4878
Xiang LingCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.
Ruojiong WangCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.
Haonan XiongCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.
Liuzhi HuCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.
Zhikun YangCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.
Hong WangCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.ORCID 0000-0003-0058-060X
Yali ZhangDepartment of Bioinformatics & Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States.
Wenjie WuDepartment of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States.
Prashant K SinghDepartment of Cancer Genetics & Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States.
Jianmin WangDepartment of Bioinformatics & Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States.
Fengzhi LiDepartment of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263, United States.
QingYong LiCollege of Pharmaceutical Sciences & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China.ORCID 0000-0003-1492-3909
Zhejiang University of Technology · CNRoswell Park Comprehensive Cancer Center · USCanget BioTekpharma (United States) · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI CANDACE S JOHNSON · 1985 to 2026
$116.6M
A small molecule broad spectrum inhibitor of antiapoptotic genes to treat cancerR44CA176937 · NCI · CANGET BIOTEKPHARMA, LLC · PI LI, FENGZHI, LING, XIANG · 2014 to 2018
$2.3M
Perform non-GLP and GLP TOX/TK studies, and file a novel drug IND with the FDA for advanced pancreatic cancer patient clinical trialsR43CA275410 · NCI · CANGET BIOTEKPHARMA, LLC · PI LI, FENGZHI, LING, XIANG · 2023 to 2023
$400k
A novel small molecule FL7N-1 for treating pediatric cancer retinoblastomaR43CA221389 · NCI · CANGET BIOTEKPHARMA, LLC · PI LI, FENGZHI, LING, XIANG · 2018 to 2018
$225k
NCI NIH HHS P30 CA016056NCI NIH HHS R43 CA221389NCI NIH HHS R43 CA275410NCI NIH HHS R44 CA176937
6 · The paper itself

Abstract

Structurally, FL118 is a camptothecin analogue and possesses exceptional antitumor efficacy against human cancer through a novel mechanism of action (MOA). In this report, we have synthesized and characterized 24 FL118 Position 7-substituted and 24 FL118 Position 9-substituted derivatives. The top compounds were further characterized for their MOA in colorectal cancer (CRC) models using CRC patient-derived xenograft (PDX) models and pancreatic cancer PDX models to evaluate their antitumor activities. Four FL118 Position 7-substituted derivatives showed significantly better antitumor efficacy than the FL118 Position 9-substituted derivatives. The four identified compounds also appeared to have better antitumor activity than their parental platform FL118. Interestingly, RNA-Seq analyses indicated that three of the four compounds exerted antitumor effects via an MOA similar to FL118, which provided an intriguing opportunity for follow-up studies. Extended in vivo studies revealed that

Indexed as

Antineoplastic AgentsIndolizinesBenzodioxolesCell Line, TumorHumansStructure-Activity Relationship7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dioneAntineoplastic AgentsBenzodioxolesIndolizines

Identifiers

PMID38100041
PMCPMC11712954
OpenAlexW4389781493

What OpenQuestion holds

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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.