ArticleJournal of clinical medicine2021
Whole-Body Pharmacokinetics and Physiologically Based Pharmacokinetic Model for Monomethyl Auristatin E (MMAE).
Article in Journal of clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Mislocalisation of FLT3-ITD receptor contributes to MV4-11 leukaemia cell resistance to antibody-drug conjugate.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Article
- Delivery of Monomethyl Auristatin E Using Ionizable Lipid Nanoparticles for B‑Cell Acute Lymphoblastic Leukemia Treatment.ACS omega · 2026Article
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning.Blood immunology & cellular therapy · 2025Article
- An aptamer-drug conjugate for promising cancer therapy with comprehensive evaluation from rodents to non-human primates.Signal transduction and targeted therapy · 2025Article
- Chemotherapy-induced neuropathy in monomethyl Auristatin E treatment: prevention by lithium.British journal of cancer · 2025Article
- Annexin A1-Targeted d-Peptide-Monomethyl Auristatin E Conjugate Enhanced Antitumor Effect of Monomethyl Auristatin E for Chemotherapy of Prostate Cancer.The Prostate · 2025Article
- Loss of RNF41 promotes bladder cancer metastasis through increasing NUDC stability to enhance tubulin polymerization.Cell death & disease · 2025Article
- Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation.Marine drugs · 2025Review
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Antibody-Drug Conjugates (ADCs): current and future biopharmaceuticals.Journal of hematology & oncology · 2025Review
- PK/PD of Positively Charged ADC in Mice.Pharmaceutics · 2025Article
- PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.The AAPS journal · 2024Article
- Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Therapeutic antibodies in oncology: an immunopharmacological overview.Cancer immunology, immunotherapy : CII · 2024Review
- Physiologically based pharmacokinetic model to predict drug-drug interactions with the antibody-drug conjugate enfortumab vedotin.Journal of pharmacokinetics and pharmacodynamics · 2024Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Monomethyl auristatin E (MMAE) is one of the most commonly used payloads for developing antibody-drug conjugates (ADC). However, limited studies have comprehensively evaluated the whole-body disposition of MMAE. Consequently, here, we have investigated the whole-body pharmacokinetics (PK) of MMAE in tumor-bearing mice. We show that while MMAE is rapidly eliminated from the plasma, it shows prolonged and extensive distribution in tissues, blood cells, and tumor. Highly perfused tissues (e.g., lung, kidney, heart, liver, and spleen) demonstrated tissue-to-plasma area under the concentration curve (AUC) ratios > 20, and poorly perfused tissues (e.g., fat, pancreas, skin, bone, and muscle) had ratios from 1.3 to 2.4. MMAE distribution was limited in the brain, and tumor had 8-fold higher exposure than plasma. A physiological-based pharmacokinetic (PBPK) model was developed to characterize the whole-body PK of MMAE, which accounted for perfusion/permeability-limited transfer of drug in the tissue, blood cell distribution of the drug, tissue/tumor retention of the drug, and plasma protein binding. The model was able to characterize the PK of MMAE in plasma, tissues, and tumor simultaneously, and model parameters were estimated with good precision. The MMAE PBPK model presented here can facilitate the development of a platform PBPK model for MMAE containing ADCs and help with their preclinical-to-clinical translation and clinical dose optimization.
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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.