ArticleBioorganic & medicinal chemistry2015
1-Benzyl-2-methyl-3-indolylmethylene barbituric acid derivatives: Anti-cancer agents that target nucleophosmin 1 (NPM1).
Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 39 citations in OpenAlex.
- An expedient metal-free cascade route to chromonyl diene scaffolds: thermodynamicRSC advances · 2022Article
- Nucleolar Proteins and Non-Coding RNAs: Roles in Renal Cancer.International journal of molecular sciences · 2021Review
- In vitro evaluation of the anticancer activity of barbituric/thiobarbituric acid-based chromene derivatives.Molecular biology reports · 2021Article
- Biobanked Glioblastoma Patient-Derived Organoids as a Precision Medicine Model to Study Inhibition of Invasion.International journal of molecular sciences · 2021Article
- Use of a molecular beacon based fluorescent method for assaying uracil DNA glycosylase (Ung) activity and inhibitor screening.Biochemistry and biophysics reports · 2021Article
- Targeting NPM1 in irradiated cells inhibits NPM1 binding to RAD51, RAD51 foci formation and radiosensitizes NSCLC.Cancer letters · 2021Article
- Nucleophosmin in Its Interaction with Ligands.International journal of molecular sciences · 2020Review
- Antifibrotic Effects of a Barbituric Acid Derivative on Liver Fibrosis by Blocking the NF-κB Signaling Pathway in Hepatic Stellate Cells.Frontiers in pharmacology · 2020Article
- Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia.Therapeutic advances in hematology · 2020Review
- A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells.Biochemistry · 2018Article
- Nucleophosmin: from structure and function to disease development.BMC molecular biology · 2016Review
- Molecules that target nucleophosmin for cancer treatment: an update.Oncotarget · 2016Review
- Development and validation of a novel assay to identify radiosensitizers that target nucleophosmin 1.Bioorganic & medicinal chemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In the present study, we have designed and synthesized a series of 1-benzyl-2-methyl-3-indolylmethylene barbituric acid analogs (7a-7h) and 1-benzyl-2-methyl-3-indolylmethylene thiobarbituric acid analogs (7 i-7 l) as nucleophosmin 1 (NPM1) inhibitors and have evaluated them for their anti-cancer activity against a panel of 60 different human cancer cell lines. Among these analogs 7 i, 7 j, and 7 k demonstrated potent growth inhibitory effects in various cancer cell types with GI50 values <2 μM. Compound 7 k exhibited growth inhibitory effects on a sub-panel of six leukemia cell lines with GI50 values in the range 0.22-0.35 μM. Analog 7 i also exhibited GI50 values <0.35 μM against three of the leukemia cell lines in the sub-panel. Analogs 7 i, 7 j, 7 k and 7 l were also evaluated against the mutant NPM1 expressing OCI-AML3 cell line and compounds 7 k and 7 l were found to cause dose-dependent apoptosis (AP50 = 1.75 μM and 3.3 μM, respectively). Compound 7k also exhibited potent growth inhibition against a wide variety of solid tumor cell lines: that is, A498 renal cancer (GI50 = 0.19 μM), HOP-92 and NCI-H522 lung cancer (GI50 = 0.25 μM), COLO 205 and HCT-116 colon cancer (GI50 = 0.20 and 0.26 μM, respectively), CNS cancer SF-539 (GI50 = 0.22 μM), melanoma MDA-MB-435 (GI50 = 0.22 μM), and breast cancer HS 578T (GI50 = 0.22 μM) cell lines. Molecular docking studies suggest that compounds 7 k and 7 l exert their anti-leukemic activity by binding to a pocket in the central channel of the NPM1 pentameric structure. These results indicate that the small molecule inhibitors 7 i, 7 j, 7 k, and 7 l could be potentially developed into anti-NPM1 drugs for the treatment of a variety of hematologic malignancies and solid tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.