Evidence map›Paper›PMID 38835128›Full record

ArticleCurrent computer-aided drug design2024

Mohammed Mouhcine, Youness Kadil, Ibtihal Segmani, Imane Rahmoune, Houda Filali

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Article in Current computer-aided drug design, 2024. 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. 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

5 authors.

Mohammed MouhcineLaboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Casablanca, Morocco.
Youness KadilLaboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Casablanca, Morocco.
Ibtihal SegmaniLaboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Casablanca, Morocco.
Imane RahmouneLaboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Casablanca, Morocco.
Houda FilaliLaboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca, Casablanca, Morocco.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundICMT (isoprenylcysteine carboxyl methyltransferase) is an enzyme that plays a key role in the post-translational modification of the K-Ras protein. The carboxyl methylation of this protein by ICMT is important for its proper localization and function. Cysmethynil (2-[5-(3-methylphenyl)-l-octyl-lH-indolo-3-yl] acetamide) causes K-Ras mislocalization and interrupts pathways that control cancer cell growth and division through inhibition of ICMT, but its poor water solubility makes it difficult and impractical for clinical use. This indicates that relatively high amounts of cysmethynil would be required to achieve an effective dose, which could result in significant adverse effects in patients.

objectiveThe general objective of this work was to find virtually new compounds that present high solubility in water and are similar to the pharmacological activity of cysmethynil. MATERIALS AND

methodsPharmacophore modeling, pharmacophore-based virtual screening, prediction of ADMET properties (absorption, distribution, metabolism, excretion, and toxicity), and water solubility were performed to recover a water-soluble molecule that shares the same chemical characteristics as cysmethynil using Discovery Studio v16.1.0 (DS16.1), SwissADME server, and pkCSM server.

resultsIn this study, ten pharmacophore model hypotheses were generated by exploiting the characteristics of cysmethynil. The pharmacophore model validated by the set test method was used to screen the "Elite Library

conclusionAccording to the results obtained, the identified compound presented a high solubility in water and could be similar to the pharmacological activity of cysmethynil.

Indexed as

Colorectal NeoplasmsProto-Oncogene Proteins p21(ras)SolubilityAcetamidesAlkyl and Aryl TransferasesAntineoplastic AgentsComputer SimulationEnzyme InhibitorsHumansIndolesMolecular Docking SimulationMutationProtein MethyltransferasesAcetamidesAlkyl and Aryl TransferasesAntineoplastic AgentsEnzyme InhibitorsIndolesKRAS protein, humanProtein Methyltransferasesprotein-S-isoprenylcysteine O-methyltransferaseProto-Oncogene Proteins p21(ras)ADMET.Colorectal cancerICMT inhibitorsKRASmolecular dockingpharmacophorevirtual screening

Identifiers

PMID38835128

What OpenQuestion holds

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Registered trials

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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.