A Series of 2‐((1‐Phenyl‐1H‐imidazol‐5‐yl)methyl)‐1H‐indoles as Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitors
Sign Up to like & getrecommendations! Published in 2021 at "ChemMedChem"
DOI: 10.1002/cmdc.202100107
Abstract: Indoleamine 2,3‐dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors for use in human cancers is now a focus of widespread research and development… read more here.
Keywords: brain penetrant; dioxygenase ido1; ido1 inhibitors; indoleamine dioxygenase ... See more keywords
Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug.
Sign Up to like & getrecommendations! Published in 2021 at "Cell reports"
DOI: 10.1016/j.celrep.2021.109957
Abstract: The highly lethal brain cancer glioblastoma (GBM) poses a daunting challenge because the blood-brain barrier renders potentially druggable amplified or mutated oncoproteins relatively inaccessible. Here, we identify sphingomyelin phosphodiesterase 1 (SMPD1), an enzyme that regulates… read more here.
Keywords: brain penetrant; targeting glioblastoma; drug; brain ... See more keywords
4-(Difluoromethyl)-5-(4-((3R,5S)-3,5-dimethylmorpholino)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a Potent, Orally Available, and Brain-Penetrant mTOR Inhibitor for the Treatment of Neurological Disorders.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c00620
Abstract: The mechanistic target of rapamycin (mTOR) pathway is hyperactivated in cancer and neurological disorders. Rapalogs and mTOR kinase inhibitors (TORKi) have recently been applied to alleviate epileptic seizures in tuberous sclerosis complex (TSC). Herein, we… read more here.
Keywords: brain penetrant; pqr626; mtor; treatment neurological ... See more keywords
Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c01498
Abstract: The G protein-coupled receptor 52 (GPR52) is an orphan receptor that is selectively expressed in the striatum and regulates various brain functions through activation of cAMP-dependent pathways. GPR52 has been identified as a promising therapeutic… read more here.
Keywords: gpr52 agonist; brain penetrant; discovery potent; penetrant gpr52 ... See more keywords
Leveraging Structure-Based Drug Design to Identify Next-Generation MAT2A Inhibitors, Including Brain-Penetrant and Peripherally Efficacious Leads.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01595
Abstract: Inhibition of the S-adenosyl methionine (SAM)-producing metabolic enzyme, methionine adenosyltransferase 2A (MAT2A), has received significant interest in the field of medicinal chemistry due to its implication as a synthetic lethal target in cancers with the… read more here.
Keywords: brain penetrant; mat2a; chemistry; mat2a inhibitors ... See more keywords
Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02078
Abstract: Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher's disease and has been suggested as a potential target for treating Parkinson's disease. Herein, we report the discovery of novel brain-penetrant GCS inhibitors.… read more here.
Keywords: gcs; glucosylceramide synthase; discovery brain; brain penetrant ... See more keywords
Discovery of a Brain Penetrant ATP-competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS disorders.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01398
Abstract: Recent clinical evaluation of Everolimus for seizure reduction in patients with Tuberous Sclerosis Complex (TSC), a disease with overactivated mTOR signaling, has demonstrated the therapeutic value of mTOR inhibitors for Central Nervous System (CNS) indications.… read more here.
Keywords: brain penetrant; inhibitor; mtor; cns disorders ... See more keywords
Characterization of the Brain Penetrant Neuropeptide Y Y2 Receptor Antagonist SF-11.
Sign Up to like & getrecommendations! Published in 2019 at "ACS chemical neuroscience"
DOI: 10.1021/acschemneuro.9b00082
Abstract: This paper discusses the biological and three-dimensional molecular structure of the novel, nonpeptide Y2R antagonist, SF-11 [ N-(4-ethoxyphenyl)-4-(hydroxydiphenylmethyl)-1-piperidinecarbothioamide]. Pharmacokinetic studies in a rat model indicated that, following intraperitoneal dosing, SF-11 crossed the blood-brain barrier and… read more here.
Keywords: brain penetrant; penetrant neuropeptide; characterization brain; brain ... See more keywords
Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.2c00272
Abstract: Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment was identified, as well… read more here.
Keywords: fragment based; brain penetrant; hdac2 inhibitor; hdac2 ... See more keywords
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Sign Up to like & getrecommendations! Published in 2022 at "Proceedings of the National Academy of Sciences of the United States of America"
DOI: 10.1073/pnas.2210442120
Abstract: Significance This study carries immediate significance and novelty from following perspectives: (a) It provides the first line of in vivo and ex vivo evidence demonstrating the crucial role of PGRN in GBA1 mutation-related diseases (i.e.,… read more here.
Keywords: penetrant pgrn; gba1 mutation; brain penetrant; pgrn ... See more keywords
Abstract 2919: Discovery of PRT811, a potent, selective, and orally bioavailable brain penetrant PRMT5 Inhibitor for the treatment of brain tumors
Sign Up to like & getrecommendations! Published in 2020 at "Cancer Research"
DOI: 10.1158/1538-7445.am2020-2919
Abstract: Protein arginine methyltransferase 5 (PRMT5) is the major type II PRMT that catalyzes the formation of symmetrical dimethyl arginine (SDMA) on protein substrates and plays important roles in regulating RNA splicing as well as transcription… read more here.
Keywords: brain penetrant; potent selective; prt811 potent; prmt5 ... See more keywords