ArticleJournal of medicinal chemistry2015
Development of novel ACK1/TNK2 inhibitors using a fragment-based approach.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Development of substituted 2-(4-(sulfonyl)piperazin-1-yl)quinazoline molecular hybrids as a new class of antimalarials.RSC advances · 2025Article
- RFX2-BNIP3 axis-driven adaptive mitophagy promotes resistance to ACK1-targeted therapy in non-small cell lung cancer.Oncogene · 2025Article
- ACK1 condensates promote STAT5 signaling in lung squamous cell carcinoma.Cancer cell international · 2025Article
- Pharmacophore Modeling of Janus Kinase Inhibitors: Tools for Drug Discovery and Exposition Prediction.Molecules (Basel, Switzerland) · 2025Article
- Novel 5-Oxopyrrolidine-3-carbohydrazides as Potent Protein Kinase Inhibitors: Synthesis, Anticancer Evaluation, and Molecular Modeling.International journal of molecular sciences · 2025Article
- Article
- ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.medRxiv : the preprint server for health sciences · 2024Article
- Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation.Molecular cancer research : MCR · 2024Article
- ACKnowledging the role of the Activated-Cdc42 associated kinase (ACK) in regulating protein stability in cancer.Small GTPases · 2023Review
- Phosphorylation of Ack1 by the Receptor Tyrosine Kinase Mer.Kinases and phosphatases · 2023Article
- Review
- Identification of Activated Cdc42-Associated Kinase Inhibitors as Potential Anticancer Agents Using Pharmacoinformatic Approaches.Biomolecules · 2023Article
- Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance.Nature communications · 2022Article
- Emerging strategies to overcome resistance to third-generation EGFR inhibitors.Journal of hematology & oncology · 2022Review
- Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting.Science translational medicine · 2022Article
- Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.Biomolecules · 2022Review
- Loss of Long Noncoding RNACancer research · 2022Article
- Synthesis and biological evaluation of novel (Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Research Progress of the Functional Role of ACK1 in Breast Cancer.BioMed research international · 2019Review
- Blockade of ACK1/TNK2 To Squelch the Survival of Prostate Cancer Stem-like Cells.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The tyrosine kinase ACK1, a critical signal transducer regulating survival of hormone-refractory cancers, is an important therapeutic target, for which there are no selective inhibitors in clinical trials to date. This work reports the discovery of novel and potent inhibitors for ACK1 tyrosine kinase (also known as TNK2) using an innovative fragment-based approach. Focused libraries were designed and synthesized by selecting fragments from reported ACK inhibitors to create hybrid structures in a mix and match process. The hybrid library was screened by enzyme-linked immunosorbent assay-based kinase inhibition and (33)P HotSpot assays. Systematic structure-activity relationship studies led to the identification of compound (R)-9b, which shows potent in vitro (IC50 = 56 nM, n = 3, (33)P HotSpot assay) and in vivo (IC50 < 2 μM, human cancer cell lines) ACK1 inhibition. Both (R)-9b and (S)-9b were stable in human plasma and displayed a long half-life (t(1/2) > 6 h).
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Registered trials
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.