ArticleBMC cancer2022
Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03917043 (A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-2449 in Patients With Advanced Solid Tumors), which is not on this map. Cited by 16 papers.
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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.
A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Orally Administered APG-2449 in Patients With Advanced Solid Tumors
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Phenotypic and genotypic characterization of single circulating tumor cells in the follow-up of high-grade serous ovarian cancer.Molecular oncology · 2026Article
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Safety, pharmacokinetic, pharmacodynamic, and efficacy properties of orally administered APG-2449 in patients with advancedEClinicalMedicine · 2025Article
- Molecular Mechanisms and Treatment Strategies of ALK-Positive Lung Cancer: A Beginner's Guide for Patients, Their Families and Carers.Thoracic cancer · 2025Review
- Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions.Biomolecules · 2025Review
- Recent advances in focal adhesion kinase (FAK)-targeting antitumor agents.RSC advances · 2025Review
- Oncogenic Mutations and the Tumor Microenvironment: Drivers of Non-Small Cell Lung Cancer Progression.Cancers · 2025Review
- Advances in Personalized Oncology.Cancers · 2024Review
- Targeting Metabolic-Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy.Antioxidants (Basel, Switzerland) · 2024Review
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/β-catenin pathway.Cell death & disease · 2023Article
- Review
- Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.Molecular therapy oncolytics · 2023Review
- Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.Frontiers in pharmacology · 2023Review
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
- Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises.Cancers · 2022Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.
methodsKINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic-pharmacodynamic correlations and the mechanism of actions driving drug combination synergy.
resultsIn mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44
conclusionsTaken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK
trial registrationClinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).
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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.