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Article

An anti-PMEL antibody-drug conjugate with a Gq/11 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial.

Nature medicine - 1 Sept 2026

Carlino Matteo S, Kapiteijn Ellen, Piperno-Neumann Sophie, Sullivan Ryan J, Carvajal Richard, Dummer Reinhard, Gromke Tanja, Hassel Jessica C, Kee Damien, Ramelyte Egle, Shoushtari Alexander N, Wei Alexander Z, Enk Alexander, Handel Eleanor E, Montazeri Kamaneh, Ramon-Patino Jorge, Richly Heike, Rodrigues Manuel, Sandhu Shahneen, Smithy James, Speetjens Frank M, Milanez-Almeida Pedro, Chaudhury Anwesha, Hoffmaster Keith, Ising Mary, Otero Javier A, RamKumar Thiruvamoor, Reynolds Aimee, Sharaby Sherif, Werner Lillian, Yerramilli-Rao Padmaja, Calvo Emiliano

Abstract excerpt

Metastatic uveal melanoma (mUM) is an aggressive cancer with limited treatment options; 85-90% of tumors harbor activating GNAQ and GNA11 mutations. Uveal melanoma cells also express PMEL (also known as PMEL17 or gp100), a melanocyte lineage antigen. DYP688, a novel biology-matched antibody-drug conjugate, binds surface PMEL and delivers the potent Gαq/Gα11 (Gq/11) inhibitor SDZ475 as payload by internalization....

Read the complete abstract on PubMed

Topics

Humans
Melanoma
Female

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

GTP-Binding Protein alpha Subunits, Gq-G11

Uveal Neoplasms

Middle Aged

Male

Aged

Immunoconjugates

Mutation

Uveal Melanoma

Adult

GTP-Binding Protein alpha Subunits

Source

Open in PubMed Open full text

Identifiers

PMID: 42443515
DOI: 10.1038/s41591-026-04518-z
PMCID: PMC13577922

Genes

GNA11
GNAQ
PMEL

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 23 Oct 2026.

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