ArticleNature communications2017
Deconvolution of Buparlisib's mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled 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.
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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Antitumor Activity of s-Triazine Derivatives: A Systematic Review.Molecules (Basel, Switzerland) · 2023Pooled it
- Stathmin guides personalized therapy in oral squamous cell carcinoma.Cancer science · 2020Trial
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- ModularFrontiers in toxicology · 2026Article
- Article
- Novel Therapies in Primary Central Nervous System Lymphoma.Clinical pharmacology : advances and applications · 2025Review
- Synthesis of Novel Derivatives of 4,6-Diarylpyrimidines and Dihydro-Pyrimidin-4-one andCurrent organic synthesis · 2025Article
- Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling.Chemical science · 2024Article
- Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities.RSC medicinal chemistry · 2024Review
- A Phase I Study of the Oral Dual-Acting Pan-PI3K/mTOR Inhibitor Bimiralisib in Patients with Advanced Solid Tumors.Cancers · 2024Article
- Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
- Antiproliferative and Tubulin-Destabilising Effects of 3-(Prop-1-en-2-yl)azetidin-2-Ones and Related Compounds in MCF-7 and MDA-MB-231 Breast Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain.bioRxiv : the preprint server for biology · 2023Article
- Computational Approaches to the Rational Design of Tubulin-Targeting Agents.Biomolecules · 2023Review
- Synthesis, Characterisation and Mechanism of Action of Anticancer 3-Fluoroazetidin-2-ones.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα.Journal of the American Chemical Society · 2022Article
- Review
- Article
- Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.Drug discovery today · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 5 countries.
Funding
Abstract
BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target effect with microtubule polymerization. Here, we developed two chemical derivatives that differ from BKM120 by only one atom. We show that these minute changes separate the dual activity of BKM120 into discrete PI3K and tubulin inhibitors. Analysis of the compounds cellular growth arrest phenotypes and microtubule dynamics suggest that the antiproliferative activity of BKM120 is mainly due to microtubule-dependent cytotoxicity rather than through inhibition of PI3K. Crystal structures of BKM120 and derivatives in complex with tubulin and PI3K provide insights into the selective mode of action of this class of drugs. Our results raise concerns over BKM120's generally accepted mode of action, and provide a unique mechanistic basis for next-generation PI3K inhibitors with improved safety profiles and flexibility for use in combination therapies.
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.