Evidence map›Paper›PMID 40200839›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2025

Design and Evaluation of Bivalent K-Ras Inhibitors That Target the CAAX Binding Site and the Acidic Surface of Farnesyltransferase and Geranylgeranyltransferase I.

Naomi Horiuchi, Rania Omer, Fumitoshi Sugino, Nanami Ogino, Yoshihisa Inoue, Kazi Aslamuzzaman, Takeyuki Suzuki, Said M Sebti, Junko Ohkanda

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2025. 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

9 authors.

Naomi HoriuchiAcademic Assembly, Institute of Agriculture, Shinshu University, 8304 Minami-Minowa, Kami-Ina, Nagano, 399-4598, Japan.
Rania OmerDepartment of Pharmacology and Toxicology, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Fumitoshi SuginoAcademic Assembly, Institute of Agriculture, Shinshu University, 8304 Minami-Minowa, Kami-Ina, Nagano, 399-4598, Japan.
Nanami OginoAcademic Assembly, Institute of Agriculture, Shinshu University, 8304 Minami-Minowa, Kami-Ina, Nagano, 399-4598, Japan.
Yoshihisa InoueSDMJ Consulting, Gohongi 2-7-8, Meguro, Tokyo, 153-0053, Japan.
Kazi AslamuzzamanDepartment of Pharmacology and Toxicology, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Takeyuki SuzukiSANKEN, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan.
Said M SebtiDepartment of Pharmacology and Toxicology, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Junko OhkandaAcademic Assembly, Institute of Agriculture, Shinshu University, 8304 Minami-Minowa, Kami-Ina, Nagano, 399-4598, Japan.ORCID https://orcid.org/0000-0001-9663-5104

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Targeting Mutant KRAS for Cancer TherapyR35CA197731 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SEBTI, SAID M · 2016 to 2022
$6.2M
JSPS 18H02106JSPS 20K21248JSPS 21H02077Massey Cancer CenterNaito FoundationNCI-designated Comprehensive Cancer Center P30CA016059NCI NIH HHS P30 CA016059NCI NIH HHS R35 CA197731Network Joint Research Center for Materials and Devices (MEXT)NIH HHS R35CA197731-01
6 · The paper itself

Abstract

Mutant K-Ras drives cancer through its membrane localization, which requires posttranslational modification by farnesyltransferase (FTase). FTase attaches farnesyl to the K-Ras C-terminal CVIM tetrapeptide, enabling membrane binding. However, K-Ras can also undergo compensatory geranylgeranylation by geranylgeranyltransferase I (GGTase I), making FTase inhibition alone ineffective. Dual inhibition of FTase and GGTase I is necessary to fully block K-Ras localization and its cancer activity. We developed bivalent inhibitors targeting both FTase and GGTase I by binding to the CVIM (C = cysteine, V = valine, I = isoleucine, M = methionine) site and an adjacent acidic surface. A nonthiol CVIM peptidomimetic based on a piperidine scaffold showed potent FTase inhibition (K

Indexed as

Alkyl and Aryl TransferasesEnzyme InhibitorsFarnesyltranstransferaseProto-Oncogene Proteins p21(ras)Binding SitesCell Line, TumorDrug DesignHumansAlkyl and Aryl TransferasesEnzyme InhibitorsFarnesyltranstransferasegeranylgeranyltransferase type-IProto-Oncogene Proteins p21(ras)bivalent inhibitorsdual inhibitionfarnesyltransferasegeranylgeranyltransferaseK‐Raspeptidomimeticsposttranslational lipid modification

Identifiers

PMID40200839
PMCPMC12080315

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.