ArticleJournal of the American Chemical Society2021
Selective CRAF Inhibition Elicits Transactivation.
Article in Journal of the American Chemical Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.Chemical reviews · 2024Review
- The Pan-RAF-MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS-MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers.Cancer discovery · 2024Article
- Targeting RAF dimers in RAS mutant tumors: From biology to clinic.Acta pharmaceutica Sinica. B · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- The sodium channel subunit SCNN1B suppresses colorectal cancer via suppression of active c-Raf and MAPK signaling cascade.Oncogene · 2023Article
- Chemogenetics of cell surface receptors: beyond genetic and pharmacological approaches.RSC chemical biology · 2022Review
- Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy.Molecules (Basel, Switzerland) · 2021Review
- A Conserved Mechanism for Hormesis in Molecular Systems.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Discovering molecules that regulate closely related protein isoforms is challenging, and in many cases the consequences of isoform-specific pharmacological regulation remains unknown. RAF isoforms are commonly mutated oncogenes that serve as effector kinases in MAP kinase signaling. BRAF/CRAF heterodimers are believed to be the primary RAF signaling species, and many RAF inhibitors lead to a "paradoxical activation" of RAF kinase activity through transactivation of the CRAF protomer; this leads to resistance mechanisms and secondary tumors. It has been hypothesized that CRAF-selective inhibition might bypass paradoxical activation, but no CRAF-selective inhibitor has been reported and the consequences of pharmacologically inhibiting CRAF have remained unknown. Here, we use bio-orthogonal ligand tethering (BOLT) to selectively target inhibitors to CRAF. Our results suggest that selective CRAF inhibition promotes paradoxical activation and exemplify how BOLT may be used to triage potential targets for drug discovery before any target-selective small molecules are known.
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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.