NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.

doi:10.1158/2159-8290.CD-24-0231

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Community

Back to search

Article

NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.

Cancer discovery - 2 Dec 2024

Lin Jessica J, Horan Joshua C, Tangpeerachaikul Anupong, Swalduz Aurélie, Valdivia Augusto, Johnson Melissa L, Besse Benjamin, Camidge D Ross, Fujino Toshio, Yoda Satoshi, Nguyen-Phuong Linh, Mizuta Hayato, Bigot Ludovic, Nobre Catline, Lee Jii Bum, Yu Mi Ra, Mente Scot, Sun Yuting, Kohl Nancy E, Porter James R, Shair Matthew D, Zhu Viola W, Felip Enriqueta, Cho Byoung Chul, Friboulet Luc, Hata Aaron N, Pelish Henry E, Drilon Alexander

Abstract excerpt

Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion-positive non-small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested. In vitro,...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Aminopyridines

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Anaplastic Lymphoma Kinase

Share to Drug Resistance, Neoplasm

Share to Lactams

Share to Lactams, Macrocyclic

Share to Protein Kinase Inhibitors

Share to Pyrazoles

Share to Xenograft Model Antitumor Assays

Source

Open in PubMed Open full text

Identifiers

PMID: 39269178
DOI: 10.1158/2159-8290.CD-24-0231
PMCID: PMC11609626

Genes

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 3 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.PMID 39269178Read ↗

TPX-0131, a Potent CNS-penetrant, Next-generation Inhibitor of Wild-type ALK and ALK-resistant Mutations.Semantic proximity Read ↗

Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer.Semantic proximity Read ↗

Lorlatinib for the treatment of ALK-positive metastatic non-small cell lung cancer.Semantic proximity Read ↗

EML4-ALK: Update on ALK InhibitorsSemantic proximity Read ↗

Structural and functional analysis of lorlatinib analogs reveals roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancerSemantic proximity Read ↗

ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Semantic proximity Read ↗

A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Semantic proximity Read ↗

TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors.Semantic proximity Read ↗

A user’s guide to lorlatinibSemantic proximity Read ↗

Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy.Semantic proximity Read ↗

Directed Therapies in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer.Semantic proximity Read ↗

Spotlight on lorlatinib and its potential in the treatment of NSCLC: the evidence to dateSemantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.