ArticleLeukemia2015
PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02885766 (A Multicenter, Open Label Cohort Phase 1 Dose Finding Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of PF-114 Mesylate for Oral Administration in Adult Patients With Philadelphia Chromosome Positive), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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 Multicenter, Open Label Cohort Phase 1 Dose Finding Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of PF-114 Mesylate for Oral Administration in Adult Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML), Which is Resistant to the 2-nd Generation Bcr-Abl Inhibitors or Has T315I Mutation in the BCR-ABL Gene
Who cites it
26 citing papers in PubMed, 64 citations in OpenAlex.
- Dose Justification for Asciminib in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia with and Without the T315I Mutation.Clinical pharmacokinetics · 2024Trial
- The Complex of Copper (II) and Zoledronic Acid: Relevance to Oxidative Death of Leukemia Cells in the Bone Marrow.International journal of molecular sciences · 2026Article
- NCIVISION: A Siamese Neural Network for Molecular Similarity Prediction MEP and RDG Images.Molecules (Basel, Switzerland) · 2025Article
- Anticancer role of Gramicidin A in myeloid leukemia.Discover oncology · 2025Article
- Phase-1 study of vamotinib (PF-114), a 3rd generation BCR::ABL1 tyrosine kinase-inhibitor, in chronic myeloid leukaemia.Annals of hematology · 2025Article
- CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells.Cell death discovery · 2025Article
- TNIK-driven regulation of ERK5 transcriptional activity in endothelial cells.Frontiers in cardiovascular medicine · 2025Article
- Discovery of 3-((3-amino-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Lyophilization Based Isolation of Exosomes.International journal of molecular sciences · 2023Article
- A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase.Journal of hematology & oncology · 2022Review
- mTORC1-Inhibition Potentiating Metabolic Block by Tyrosine Kinase Inhibitor Ponatinib in Multiple Myeloma.Cancers · 2022Article
- Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.Cancers · 2021Review
- Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1Annals of hematology · 2021Article
- Review of New-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.Current oncology reports · 2021Review
- Third-line therapy for chronic myeloid leukemia: current status and future directions.Journal of hematology & oncology · 2021Review
- Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.International journal of molecular sciences · 2021Review
- A Small Molecule Inhibitor, OGP46, Is Effective against Imatinib-Resistant BCR-ABL Mutations via the BCR-ABL/JAK-STAT Pathway.Molecular therapy oncolytics · 2020Article
- Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.Journal of clinical medicine · 2020Review
- The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML.Nature reviews. Cancer · 2020Review
- An Imatinib-non-responsive patient with anClinical case reports · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the 'gatekeeper' mutation T315I. However, a broad spectrum of kinase inhibition increases the off-target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of (i) targeting T315I and other resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114 inhibited BCR/ABL and clinically important mutants including T315I at nanomolar concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long-term cultures that either displayed nonmutational resistance or harbor the T315I. In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft models of primary Ph+ leukemia harboring the T315I, PF-114 significantly prolonged survival to a similar extent as ponatinib. Our work supports clinical evaluation of PF-114 for the treatment of resistant Ph+ leukemia.
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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.