ArticleCurrent medicinal chemistry2011
Tumor physiology and charge dynamics of anticancer drugs: implications for camptothecin-based drug development.
Article in Current medicinal chemistry, 2011. 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, 60 citations in OpenAlex.
- Potential medical applicability of N-β-Ala and N-His dipeptidomimetics against breast cancer: short in vitro and in silico screening.Scientific reports · 2026Article
- Spheroids and organoids derived from colorectal cancer as tools forExploration of targeted anti-tumor therapy · 2024Review
- Predictive Potential of Acido-Basic Properties, Solubility and Food on Bioequivalence Study Outcome: Analysis of 128 Studies.Drugs in R&D · 2023Article
- Composite Hydrogels with Included Solid-State Nanoparticles Bearing Anticancer Chemotherapeutics.Gels (Basel, Switzerland) · 2023Review
- Nanoscale Surface-Enhanced Raman Spectroscopy Investigation of a Polyphenol-Based Plasmonic Nanovector.Nanomaterials (Basel, Switzerland) · 2023Article
- Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy.Science advances · 2022Article
- PSMA-Targeting Imaging and Theranostic Agents-Current Status and Future Perspective.International journal of molecular sciences · 2022Review
- Chimeric Antigen Receptor (CAR) T Cell Therapy for Glioblastoma.Cancer treatment and research · 2022Review
- Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics.Cancer cell international · 2021Article
- Dual responsive PMEEECL-PAE block copolymers: a computational self-assembly and doxorubicin uptake study.RSC advances · 2020Article
- DNA topoisomerase-targeting chemotherapeutics: what's new?Cancer chemotherapy and pharmacology · 2017Review
- Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma.Pharmaceutical research · 2016Review
- In vivo tumour extracellular pH monitoring using electron paramagnetic resonance: the effect of X-ray irradiation.NMR in biomedicine · 2014Article
- Targeting ion transport in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Article
- The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts.International journal of molecular imaging · 2013Article
- Design of High-Specificity Nanocarriers by Exploiting Non-Equilibrium Effects in Cancer Cell Targeting.PloS one · 2013Article
- Cancer nanomedicines targeting tumor extracellular pH.Colloids and surfaces. B, Biointerfaces · 2012Review
- The Valley of Death in anticancer drug development: a reassessment.Trends in pharmacological sciences · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Charge is an important characteristic of drug molecules, since ionization sites determine the pKa at a particular pH. The pKa in turn can affect many parameters, including solubility, dissolution rate, reaction kinetics, formulation, cell permeability, tissue distribution, renal elimination, metabolism, protein binding and receptor interactions. The impact of charge dynamics is amplified in human solid tumors that exhibit the glycolytic phenotype and associated acidic extracellular microenvironment. This phenotype is driven by hypoxia and creates a pH gradient in tumors that favors uptake of weak acids and exclusion of weak bases. Established anticancer drugs exhibit a range of pKa's and thus variable ability to exploit the tumor pH gradient. The camptothecins are a prime example as they represent a diverse class of approved anticancer drugs and drug candidates whose charge distribution varies with pH. An in silico method was used to predict charge distribution of camptothecins at physiological versus acidic pH in both the lactone and carboxylate forms. A significant amount of uncharged carboxylate was predicted at acidic pH that could enter tumor cells and accumulate in mitochondria to inhibit mitochondrial topoisomerase I. A model is presented to describe the charge dynamics of a new camptothecin analog and the impact on nuclear and mitochondrial mechanism(s) of action. This example illustrates the importance of integrating tumor physiology and charge dynamics into anticancer drug development.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.