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    DRUG CLASS:

    LRRK2 inhibitor

    Related drugs:
    1m
    ALK Inhibition Prolongs Survival in a Mouse Model of ALK-Positive Anaplastic Thyroid Cancer. (PubMed, Thyroid)
    Treatment of primary Trp53KO/ALKF1174L ATC cells with the ALK inhibitor TAE-684 decreased AKT and ERK phosphorylation and induced a dose-dependent cytotoxicity...This study provides the first functional data supporting the use of ALK inhibitors in patients with ALK-driven ATC. Our novel ATC mouse model and the derived cell lines offer valuable tools to explore the molecular characteristics of ATC, especially signaling pathway activation and tumor microenvironment, and to test novel therapeutics for the treatment of advanced thyroid cancers.
    Preclinical • Journal
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    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
    |
    TP53 mutation • ALK positive • ALK rearrangement
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    TAE-684
    5ms
    Restoration of Lysosomal Hydrolase Activities by LRRK2 Inhibition in GBA1- and LRRK2-Associated Parkinson's Disease Patient-Derived Cells. (PubMed, J Neurochem)
    Moreover, LRRK2 inhibition also enhances the activity of other lysosomal hydrolases. Our findings expand the understanding of the molecular mechanism of LRRK2 inhibitors, offering valuable insights for further development of PD treatments.
    Journal
    |
    CTSD (Cathepsin D) • LAMP2 (Lysosomal Associated Membrane Protein 2) • LRRK2 (Leucine Rich Repeat Kinase 2)
    5ms
    Identification of biomarkers based on ubiquitin-correlated genes for predicting immune profile and drug sensitivity in lung adenocarcinoma. (PubMed, Front Pharmacol)
    The medications TAE684, Cisplatin, and Midostaurin exhibited the largest negative correlation with Riskscore, according to drug sensitivity study. Lastly, we demonstrated through in vitro tests that HEATR1 knockdown markedly reduced LUAD cell survival, migration, and invasion. This study is the first to systematically integrate the ubiquitin pathway with multi-omics data, constructing a robust risk model for LUAD prognosis and immune characteristics, providing a theoretical reference for future exploration of potential biomarkers for LUAD patients' diagnosis.
    Journal • IO biomarker
    |
    FAT1 (FAT atypical cadherin 1)
    |
    cisplatin • midostaurin • TAE-684
    7ms
    SLC34A2 inhibits tumorigenesis and progression via upregulating LRRK2/TTF-1/SELENBP1 axis in lung adenocarcinoma. (PubMed, Cancer Gene Ther)
    In summary, our current research revealed a novel SLC34A2/LRRK2/TTF-1/SELENBP1 axis and its involvement in inhibiting the malignant characteristics of LUAD cells for the first time, which made contribution to further exploring the clinical application of SLC34A2. Furthermore, it also might offer novel insights into understanding how AT2 cells undergo malignant transformation into LUAD cells in the future.
    Journal
    |
    SLC34A2 (Solute carrier family 34 member 2) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • LRRK2 (Leucine Rich Repeat Kinase 2)
    8ms
    Study to Evaluate HT-4253 in Healthy Subjects (clinicaltrials.gov)
    P1, N=80, Completed, Halia Therapeutics, Inc. | Recruiting --> Completed
    Trial completion
    9ms
    LUMA: A Study to Learn About the Safety of BIIB122 Tablets and Whether They Can Slow the Worsening of Early-Stage Parkinson's Disease in Adults Between the Ages of 30 and 80 (clinicaltrials.gov)
    P2, N=650, Active, not recruiting, Biogen | Recruiting --> Active, not recruiting
    Enrollment closed
    9ms
    A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered ZE75-0267 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of ZE75-0267 in Healthy Volunteers (ACTRN12624001426572)
    P1, N=64, Recruiting, Brenig Therapeutics AU Pty Ltd. (subsidiary of Brenig Therapeutics ) | Not yet recruiting --> Recruiting
    Enrollment open • Trial initiation date
    10ms
    Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications. (PubMed, Med Chem)
    Additionally, the LRRK2 antagonist MLi-2 demonstrated remarkable efficacy in treating neurodegenerative diseases, while indazole-5-carboxamides exhibited a strong affinity for monoamine oxidases, potentially offering new therapeutic options for Parkinson's disease. Inhibition of COX-2 and FGFR resulted in anti-inflammatory effects, with minimal off-target damage observed in vivo. Collectively, our findings underscore the therapeutic versatility of indazole frameworks across various disease pathways, suggesting their potential for developing innovative treatments for cancer, infections, metabolic disorders, and neurological conditions.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • KDR (Kinase insert domain receptor) • CDK2 (Cyclin-dependent kinase 2) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • LRRK2 (Leucine Rich Repeat Kinase 2)
    |
    HER-2 positive
    1year
    NEULARK: A Phase 2 Study of NEU-411 in Companion Diagnostic-Positive Participants with Early Parkinson's Disease (clinicaltrials.gov)
    P2, N=150, Recruiting, Neuron23 Inc. | Not yet recruiting --> Recruiting
    Enrollment open • Companion diagnostic
    1year
    A Phase 1, SAD and MAD Study to Evaluate the Safety and Tolerability of FB418 (clinicaltrials.gov)
    P1, N=64, Recruiting, 1ST Biotherapeutics, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2024 --> Dec 2024
    Enrollment open • Trial primary completion date
    1year
    NEULARK: A Phase 2 Study of NEU-411 in Companion Diagnostic-Positive Participants with Early Parkinson's Disease (clinicaltrials.gov)
    P2, N=150, Not yet recruiting, Neuron23 Inc.
    New P2 trial • Companion diagnostic
    over1year
    Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's Disease (LRRK2-PD) (clinicaltrials.gov)
    P2, N=50, Recruiting, Denali Therapeutics Inc. | Not yet recruiting --> Recruiting
    Enrollment open