Halogenation at the Phenylalanine Residue of Monomethyl Auristatin F Leads to a Favorable

Iris K Sokka, Surachet Imlimthan, Mirkka Sarparanta, Hannu Maaheimo, Mikael P Johansson, Filip S Ekholm

Open access · hybridAbstract read

In one paragraph

Article in Molecular pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it

0cells of the map it votes in

3citing papers in PubMed

0.2field-weighted citation impact, top 57% of its field

1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 citations in OpenAlex.

Advancements in Dual-Load Antibody-Drug Conjugates and Challenges with Quality Analysis.Pharmaceuticals (Basel, Switzerland) · 2026
Review
Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026
Review
Click Chemistry-Generated Auristatin F-Linker-Benzylguanine for a SNAP-Tag-Based Recombinant Antibody-Drug Conjugate Demonstrating Selective Cytotoxicity toward EGFR-Overexpressing Tumor Cells.ACS omega · 2023
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Iris K SokkaDepartment of Chemistry, University of Helsinki, P.O. Box 55, A. I. Virtasen aukio 1, FI-00014 Helsinki, Finland.ORCID 0000-0002-5148-4987

Surachet ImlimthanDepartment of Chemistry, University of Helsinki, P.O. Box 55, A. I. Virtasen aukio 1, FI-00014 Helsinki, Finland.ORCID 0000-0003-2520-2146

Mirkka SarparantaDepartment of Chemistry, University of Helsinki, P.O. Box 55, A. I. Virtasen aukio 1, FI-00014 Helsinki, Finland.ORCID 0000-0002-2956-4366

Hannu MaaheimoVTT Technical Research Centre of Finland Ltd, P.O. Box 1000, VTT, FI-02044 Espoo, Finland.

Mikael P JohanssonDepartment of Chemistry, University of Helsinki, P.O. Box 55, A. I. Virtasen aukio 1, FI-00014 Helsinki, Finland.ORCID 0000-0002-9793-8235

Filip S EkholmDepartment of Chemistry, University of Helsinki, P.O. Box 55, A. I. Virtasen aukio 1, FI-00014 Helsinki, Finland.ORCID 0000-0002-4461-2215

University of Helsinki · FIVTT Technical Research Centre of Finland · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Halogenation can be utilized for the purposes of labeling and molecular imaging, providing a means to, e.g., follow drug distribution in an organism through positron emission tomography (PET) or study the molecular recognition events unfolding by nuclear magnetic resonance (NMR) spectroscopy. For cancer therapeutics, where often highly toxic substances are employed, it is of importance to be able to track the distribution of the drugs and their metabolites in order to ensure minimal side effects. Labeling should ideally have a negligible disruptive effect on the efficacy of a given drug. Using a combination of NMR spectroscopy and cytotoxicity assays, we identify a site susceptible to halogenation in monomethyl auristatin F (MMAF), a widely used cytotoxic agent in the antibody-drug conjugate (ADC) family of cancer drugs, and study the effects of fluorination and chlorination on the physiological solution structure of the auristatins and their cytotoxicity. We find that the cytotoxicity of the parent drug is retained, while the conformational equilibrium is shifted significantly toward the biologically active

Indexed as

HalogenationAminobenzoatesAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalCytotoxinsHumansImmunoconjugatesIsomerismMagnetic Resonance SpectroscopyMiceMolecular ConformationNeoplasmsOligopeptidesPhenylalanineAminobenzoatesAntineoplastic AgentsauristatinCytotoxinsImmunoconjugatesmonomethylauristatin FOligopeptidesPhenylalanineantibody−drug conjugatesauristatinscancer therapeuticsNMR-spectroscopystructural characterization

Identifiers

PMID34296616

DOI10.1021/acs.molpharmaceut.1c00342

PMCPMC8397390

OpenAlexW3184783728

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Registered trials

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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.