Evidence map›Paper›PMID 41482524›Full record

ArticleNature cancer2026

The MEK-RAF molecular glue IK-595 has potent antitumor activity across RAS/MAPK pathway-altered cancers.

Eric Haines, Michael Burke, Rachel Catterall, Victor De Jesus, Daniel Hidalgo, Bin Li, Joseph D Manna, Ao Yang, Jill Cavanaugh, Sarah R Wessell and 7 more

Abstract read
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In one paragraph

Article in Nature cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

17 authors.

Eric HainesIkena Oncology, Inc., Boston, MA, USA.
Michael BurkeDelphia Therapeutics, Cambridge, MA, USA.
Rachel CatterallRosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Victor De JesusAiRNA One Kendall Square, Cambridge, MA, USA.
Daniel HidalgoAktis Oncology, Boston, MA, USA.
Bin LiAlkermes 852 Winter Street, Waltham, MA, USA.
Joseph D MannaDelphia Therapeutics, Cambridge, MA, USA.
Ao YangQuotient Therapeutics, Cambridge, MA, USA.
Jill CavanaughBristol Myers Squibb, East Cambridge, MA, USA.
Sarah R WessellBPGbio Inc, Framingham, MA, USA.
Marta Sanchez-MartinAktis Oncology, Boston, MA, USA.
Alexander IvlievRemix Therapeutics, Watertown, MA, USA.
Wilmin BartoliniIkena Oncology, Inc., Boston, MA, USA.
Sergio SantillanaSolu Therapeutics, Boston, MA, USA.
Jeffrey EcsedyIkena Oncology, Inc., Boston, MA, USA. jecsedy@ikenaoncology.com.ORCID http://orcid.org/0000-0002-4232-5490
Michelle X ZhangStipple Bio, Cambridge, MA, USA.
Sabine K RuppelSerinus Biosciences, New York, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MAPK pathway alterations are the most common oncogenic drivers. Among the approved therapies targeting this pathway are RAS, MEK and RAF inhibitors. However, therapeutic resistance and toxicities have limited their clinical success. Here, to overcome these liabilities, we developed IK-595, a potent MEK-RAF molecular glue. IK-595 traps MEK in an inactive complex with all RAF isoforms. In addition, IK-595 precludes CRAF-mediated MEK reactivation and ARAF heterodimerization, allowing for prolonged target engagement and durable MAPK pathway inhibition. This translates into superior antitumor activity across a wide range of cancer model indications harboring MAPK pathway alterations. A key advantage of IK-595 is its ability to achieve transient high plasma exposure affording a larger therapeutic window. The unique mechanism of action and improved tolerability positions IK-595 as an ideal combination partner. IK-595 is an MEK-RAF molecular glue that prolongs pathway inhibition while providing a broader therapeutic window as monotherapy and in combination.

Indexed as

Antineoplastic AgentsMAP Kinase Signaling SystemMitogen-Activated Protein Kinase KinasesNeoplasmsProtein Kinase Inhibitorsraf Kinasesras ProteinsAnimalsCell Line, TumorFemaleHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsMitogen-Activated Protein Kinase KinasesProtein Kinase Inhibitorsraf Kinasesras Proteins

Identifiers

PMID41482524

What OpenQuestion holds

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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.