Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c01725
Abstract: PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA;… read more here.
Keywords: parp; methyl; parp1; cns penetrant ... See more keywords
Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors.
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DOI: 10.1021/acsmedchemlett.2c00081
Abstract: Inhibition of histone deacetylase 6 (HDAC6) in the brain is a highly attractive therapeutic target for the treatment of neurodegenerative diseases. The low blood-brain barrier permeability of most known HDAC6 inhibitors, however, prevents their application… read more here.
Keywords: cns penetrant; hdac6 inhibitors; histone deacetylase; benzylpiperazine derivatives ... See more keywords
Discovery of ONO-TR-772 (VU6018042): A Highly Selective and CNS Penetrant TREK Inhibitor in Vivo Tool Compound
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DOI: 10.1021/acsmedchemlett.5c00215
Abstract: Herein we describe our continuing work on the K2P family of potassium ion channels with the chemical optimization of a selective and CNS penetrant series of TREK inhibitors, culminating in the discovery of ONO-TR-772 (VU6018042).… read more here.
Keywords: selective cns; ono 772; trek; cns penetrant ... See more keywords
First-in-human trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of zagociguat (CY6463), a CNS-penetrant soluble guanylyl cyclase stimulator.
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DOI: 10.1111/cts.13537
Abstract: Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate play a role in learning and memory formation. Zagociguat (CY6463) is a novel stimulator of sGC being developed for the treatment of neurodegenerative disease. Single… read more here.
Keywords: stimulator; cyclase; cns; zagociguat cy6463 ... See more keywords
Abstract 5719: Identification of EIK1004 (IMP1707), a CNS-penetrant, potent, and selective PARP1 inhibitor poised for testing in patients with HRD mutant tumors
Sign Up to like & getrecommendations! Published in 2025 at "Cancer Research"
DOI: 10.1158/1538-7445.am2025-5719
Abstract: Nonselective poly(ADP-ribose) polymerase (PARP) inhibitors have proven to be effective in patients whose tumors harbor mutations in DNA repair proteins, although their efficacy is hampered by dose reductions and suspensions due to on-target toxicity resulting… read more here.
Keywords: brain; mda 436; parp1; cns penetrant ... See more keywords
Abstract LB240: Preclinical evaluation of ABSK112, a selective and CNS-penetrant compound with strong HER2 inhibitory activity for treating HER2-driven solid tumors
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DOI: 10.1158/1538-7445.am2025-lb240
Abstract: HER2+ cancers, driven by the overexpression or amplification of the HER2 oncogene, are prevalent in various malignancies, including breast, gastric, and lung cancers. These tumors are often associated with a heightened risk of brain metastases.… read more here.
Keywords: selective cns; cns penetrant; her2; her2 driven ... See more keywords