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Article

Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology.

Journal of medicinal chemistry - 14 May 2020

Moccia Marialuisa, Frett Brendan, Zhang Lingtian, Lakkaniga Naga Rajiv, Briggs David C, Chauhan Rakhee, Brescia Annalisa, Federico Giorgia, Yan Wei, Santoro Massimo, McDonald Neil Q, Li Hong-Yu, Carlomagno Francesca

Abstract excerpt

RET receptor tyrosine kinase is a driver oncogene in human cancer. We recently identified the clinical drug candidate Pz-1, which targets RET and VEGFR2. A key in vivo metabolite of Pz-1 is its less active demethylated pyrazole analogue. Using bioisosteric substitution methods, here, we report the identification of NPA101.3, lacking the structural liability for demethylation. NPA101.3 showed a selective...

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Identifiers

PMID: 32298114
DOI: 10.1021/acs.jmedchem.9b01336
PMCID: PMC7901654

Genes

RET
HRAS

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 6 Sept 2026. Manifest publication-graph-cohort-2026-09-06.1.

Source receipt: pubmed, retrieved 6 Sept 2026.

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