Evidence map›Paper›PMID 41244592›Full record

ArticleiScience2025

DIRAS3-derived cyclic peptides disrupt KRAS-RAF interaction and KRAS nanoclustering, suppressing KRAS-driven pancreatic and ovarian tumors.

Joshua P Gray, Gamze Bildik, Ha-Neul Kim, Margie N Sutton, Jing Wang, Amarachi O Osuji, Nefeli Batistatou, Hailing Yang, Weiqun Mao, Zhi Tan and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. 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

19 authors.

Joshua P GrayDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Gamze BildikDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Ha-Neul KimPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Margie N SuttonDepartment of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jing WangDepartment of Chemistry, Tufts University, Medford, MA 02155, USA.
Amarachi O OsujiDepartment of Chemistry, Tufts University, Medford, MA 02155, USA.
Nefeli BatistatouDepartment of Chemistry, Tufts University, Medford, MA 02155, USA.
Hailing YangDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Weiqun MaoDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Zhi TanDepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Geneviève M C Gasmi-SeabrookPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Junchen LiuDepartment of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
John F HancockDepartment of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Christopher B MarshallPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Joshua A KritzerDepartment of Chemistry, Tufts University, Medford, MA 02155, USA.
Mitsuhiko IkuraPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Robert C BastDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Steven W MillwardDepartment of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Zhen LuDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

Funding

The University of Texas MD Anderson Cancer Center SPORE in Ovarian CancerP50CA281701 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ROBERT C BAST, ANIL K SOOD · 2023 to 2026
$11.5M
Diversity Supplement for Imani McDonald - Developing Autophagy-Targeting Chimeras and Optimizing Cell Penetration of Large-Molecule TherapeuticsR35GM148407 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI Joshua A Kritzer · 2023 to 2026
$2.6M
NCI NIH HHS P50 CA281701NIGMS NIH HHS R35 GM148407
6 · The paper itself

Abstract

Mutations in KRAS drive 88% of pancreatic ductal adenocarcinomas (PDAC) and up to 40% of low-grade serous ovarian cancers (LGSOC), making KRAS a long-standing therapeutic target. We previously showed that DIRAS3 binds RAS, forming heterodimers that disrupt RAS clustering and downstream MAPK signaling. Building on this, we developed conformationally constrained DIRAS3-derived peptides using two cyclization strategies and characterized them by NMR and biolayer interferometry. These cyclic peptides attenuate the interaction between KRAS and the BRAF RAS-binding domain, penetrate cells efficiently, and inhibit KRAS nanoclustering on the inner leaflet of the plasma membrane. Functionally, they reduce cell viability and suppress PDAC and LGSOC growth in cell culture and xenograft models. Our findings demonstrate that DIRAS3-based cyclic peptides represent a distinct strategy to directly inhibit oncogenic KRAS signaling and provide a promising framework for therapeutic development in KRAS-driven cancers.

Indexed as

cancermolecular biologystructural biology

Identifiers

PMID41244592
PMCPMC12616096

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.