Evidence map›Paper›PMID 36599039›Full record

ArticleJournal of medicinal chemistry2023

Application of a Biocatalytic Strategy for the Preparation of Tiancimycin-Based Antibody-Drug Conjugates Revealing Key Insights into Structure-Activity Relationships.

Andrew D Steele, Alexander F Kiefer, Dobeen Hwang, Dong Yang, Christiana N Teijaro, Ajeeth Adhikari, Christoph Rader, Ben Shen

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Chemical Tagging ofJournal of the American Chemical Society · 2025
    Article
  4. Article
  5. 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

8 authors.

Alexander F KieferORCID 0000-0002-4540-6501
Dobeen Hwang
Christiana N Teijaro
Ajeeth AdhikariSkaggs Graduate School of Chemical and Biological Sciences, Scripps Research, Jupiter, Florida 33458, United States.
Christoph RaderSkaggs Graduate School of Chemical and Biological Sciences, Scripps Research, Jupiter, Florida 33458, United States.ORCID 0000-0001-9955-3454
Ben ShenSkaggs Graduate School of Chemical and Biological Sciences, Scripps Research, Jupiter, Florida 33458, United States.ORCID 0000-0002-9750-5982

Funding

Mining Actinomycetal Genomes for Natural Product Discovery and BiosynthesisR35GM134954 · NIGMS · UNIVERSITY OF FLORIDA · PI Ben Shen · 2020 to 2026
$5.1M
Novel Enediyne-Based Antibody-Drug Conjugates for CancersR01CA204484 · NCI · UNIVERSITY OF FLORIDA · PI Natarajan Muthusamy, Ben Shen · 2017 to 2026
$4.6M
NCI NIH HHS R01 CA204484NIGMS NIH HHS R35 GM134954
6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) are cancer chemotherapeutics that utilize a monoclonal antibody (mAb)-based delivery system, a cytotoxic payload, and a chemical linker. ADC payloads must be strategically functionalized to allow linker attachment without perturbing the potency required for ADC efficacy. We previously developed a biocatalytic system for the precise functionalization of tiancimycin (TNM)-based payloads. The TNMs are anthraquinone-fused enediynes (AFEs) and have yet to be translated into the clinic. Herein, we report the translation of biocatalytically functionalized TNMs into ADCs in combination with the dual-variable domain (DVD)-mAb platform. The DVD enables both site-specific conjugation and a plug-and-play modularity for antigen-targeting specificity. We evaluated three linker chemistries in terms of TNM-based ADC potency and antigen selectivity, demonstrating a trade-off between potency and selectivity. This represents the first application of AFE-based payloads to DVDs for ADC development, a workflow that is generalizable to further advance AFE-based ADCs for multiple cancer types.

Indexed as

Antineoplastic AgentsImmunoconjugatesNeoplasmsAntibodies, MonoclonalHumansStructure-Activity RelationshipAntibodies, MonoclonalAntineoplastic AgentsImmunoconjugates

Identifiers

PMID36599039
PMCPMC11660660

What OpenQuestion holds

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Registered trials

None linked

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.