ReviewMedicinal research reviews2022
Mechanism of activation and the rewired network: New drug design concepts.
Review in Medicinal research reviews, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Tumors and their microenvironments: Learning from pediatric brain pathologies.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- Ras, RhoA, and vascular pharmacology in neurodevelopment and aging.Neurochemistry international · 2024Review
- Unveiling hidden connections in omics data via pyPARAGON: an integrative hybrid approach for disease network construction.Briefings in bioinformatics · 2024Article
- CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.JACS Au · 2024Article
- 1,4-Diaryl-1,2,3-triazole neolignan-celecoxib hybrids inhibit experimental arthritis induced by zymosan.Inflammopharmacology · 2023Article
- Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK.Biophysical reviews · 2023Review
- Pan-cancer clinical impact of latent drivers from double mutations.Communications biology · 2023Article
- A New View of Activating Mutations in Cancer.Cancer research · 2022Article
- Review
- The mechanism of activation of MEK1 by B-Raf and KSR1.Cellular and molecular life sciences : CMLS · 2022Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Regulatory spine RS3 residue of protein kinases: a lipophilic bystander or a decisive element in the small-molecule kinase inhibitor binding?Biochemical Society transactions · 2022Article
- Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.Pharmaceutics · 2022Review
- Understanding the P-Loop Conformation in the Determination of Inhibitor Selectivity Toward the Hepatocellular Carcinoma-Associated Dark Kinase STK17B.Frontiers in molecular biosciences · 2022Article
- Allosteric regulation of autoinhibition and activation of c-Abl.Computational and structural biotechnology journal · 2022Article
- Mechanistic insights into the clinical Y96D mutation with acquired resistance to AMG510 in the KRASFrontiers in oncology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Precision oncology benefits from effective early phase drug discovery decisions. Recently, drugging inactive protein conformations has shown impressive successes, raising the cardinal questions of which targets can profit and what are the principles of the active/inactive protein pharmacology. Cancer driver mutations have been established to mimic the protein activation mechanism. We suggest that the decision whether to target an inactive (or active) conformation should largely rest on the protein mechanism of activation. We next discuss the recent identification of double (multiple) same-allele driver mutations and their impact on cell proliferation and suggest that like single driver mutations, double drivers also mimic the mechanism of activation. We further suggest that the structural perturbations of double (multiple) in cis mutations may reveal new surfaces/pockets for drug design. Finally, we underscore the preeminent role of the cellular network which is deregulated in cancer. Our structure-based review and outlook updates the traditional Mechanism of Action, informs decisions, and calls attention to the intrinsic activation mechanism of the target protein and the rewired tumor-specific network, ushering innovative considerations in precision medicine.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.