JYP0322, a highly selective and brain-penetrant ROS1 inhibitor, overcomes ROS1G2032R resistance mutation in NSCLC: The first-in-human phase 1 trial.

doi:10.1016/j.ccell.2026.03.018

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

JYP0322, a highly selective and brain-penetrant ROS1 inhibitor, overcomes ROS1G2032R resistance mutation in NSCLC: The first-in-human phase 1 trial.

Cancer cell - 11 May 2026

Ma Yuxiang, Xue Jinhui, Gao Fangfang, Yang Yunpeng, Zhao Yuanyuan, Wang Linlin, Huang Zhangzhou, Wu Chunjiao, Luo Yongzhong, Li Juan, Fang Jian, Song Zhengbo, Li Yongsheng, Ma Huiwen, Guo Qinxiang, Yi Tienan, Liu Xiting, Liu Zhihua, Zhou Jianya, Dong Xiaorong, Yu Qitao, He Jianbo, Yang Liuzhong, Fang Wenfeng, Sun Yuping, Qi Yaling, Lv Jing, Ge Zhen, Xia Binyan, Li Lei, Wang Wei, Huang Yan, Zhang Li, Zhao Hongyun

Abstract excerpt

Targeted therapies against ROS1-rearrangements face limitations due to resistance mutations, brain metastases, and central nervous system toxicities. We have developed a next-generation, brain-penetrant ROS1 inhibitor, JYP0322, that can overcome resistance mutations (e.g., ROS1G2032R) while minimizing off-target inhibition. In preclinical studies, JYP0322 demonstrated >130-fold selectivity over TRKA, potent...

Read the complete abstract on PubMed

Topics

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

Share to Brain Neoplasms

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

Share to Carcinoma, Non-Small-Cell Lung

Share to Drug Resistance, Neoplasm

Share to Protein-Tyrosine Kinases

Share to Proto-Oncogene Proteins

Share to Receptor, trkA

Share to Tyrosine Kinase Inhibitors

Share to Xenograft Model Antitumor Assays

Source

Open in PubMed

Identifiers

PMID: 42030931
DOI: 10.1016/j.ccell.2026.03.018

Genes

ROS1

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

JYP0322, a highly selective and brain-penetrant ROS1 inhibitor, overcomes ROS1G2032R resistance mutation in NSCLC: The first-in-human phase 1 trial.PMID 42030931Read ↗

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.Semantic proximity Read ↗

The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical modelsSemantic proximity Read ↗

NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations.Semantic proximity Read ↗

Comprehensive Review of ROS1 Tyrosine Kinase Inhibitors-Classified by Structural Designs and Mutation Spectrum (Solvent Front Mutation [G2032R] and Central β-Sheet 6 [Cβ6] Mutation [L2086F]).Semantic proximity Read ↗

SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.Semantic proximity Read ↗

ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current PerspectivesSemantic proximity Read ↗

ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to DateSemantic proximity Read ↗

Acquired MET D1228N Mutations Mediate Crizotinib Resistance in Lung Adenocarcinoma with ROS1 Fusion: A Case Report.Semantic proximity Read ↗

Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant MutationsSemantic proximity Read ↗

Crizotinib in <i>ROS1</i>-Rearranged Non–Small-Cell Lung CancerSemantic proximity Read ↗

Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.Semantic proximity Read ↗

Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase InhibitorsSemantic proximity Read ↗

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