A5032388871- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Bipolar Disorder and Treatment
- Glycosylation and Glycoproteins Research
- Schizophrenia research and treatment
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Magnetic and transport properties of perovskites and related materials
- Adenosine and Purinergic Signaling
- Immunotherapy and Immune Responses
- Photochromic and Fluorescence Chemistry
- Nicotinic Acetylcholine Receptors Study
- Nanoparticle-Based Drug Delivery
- Neuroendocrine regulation and behavior
- Pharmacological Effects and Toxicity Studies
- Electroconvulsive Therapy Studies
- RNA Interference and Gene Delivery
- Polyomavirus and related diseases
- Synthesis and pharmacology of benzodiazepine derivatives
- Erythropoietin and Anemia Treatment
- Fluid Dynamics and Turbulent Flows
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
Fujifilm (Japan)
2018-2023
GlaxoSmithKline (Japan)
2017-2022
GlaxoSmithKline (United Kingdom)
2014-2015
Food Research Institute
2000-2009
Kyoto University
1998-2008
The University of Tokyo
1995-2006
Merck & Co., Inc., Rahway, NJ, USA (United States)
1999-2003
Wee1 is a tyrosine kinase that phosphorylates and inactivates CDC2 involved in G(2) checkpoint signaling. Because p53 key regulator the G(1) checkpoint, p53-deficient tumors rely only on after DNA damage. Hence, such are selectively sensitized to DNA-damaging agents by inhibition. Here, we report discovery of potent selective small-molecule inhibitor kinase, MK-1775. This compound inhibits phosphorylation at Tyr15 (CDC2Y15), direct substrate cells. MK-1775 abrogates damage leading apoptosis...
The thermally induced insulator-metal transition (IMT) has been investigated for single crystals of undoped and lightly doped ${\mathrm{LaCoO}}_{3}$ by measurements the optical-conductivity spectra, resistivity, Hall coefficient up to 800 K. IMT around 500 K, where spin-state from nonmagnetic $(S=0)$ ground state intermediate-spin $(S=1)$ is nearly completed, characterized a large energy-scale change electronic structure as well steep increase carrier number typical metallic value due...
The functional roles of metabotropic glutamate receptor (mGluR) 1 in integrative brain functions were investigated using a potent and selective mGluR1 allosteric antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1<i>H</i>-1,2,3-triazol-4-yl]-<i>N</i>-isopropyl-<i>N</i>-methyl-3,6-dihydropyridine-1(2<i>H</i>)-carboxamide], comparison with the mGluR5 antagonist mGluR2/3 orthosteric agonist rodents. reduced maternal separation-induced ultrasonic vocalization stress-induced hyperthermia...
A highly potent and selective metabotropic glutamate receptor (mGluR) 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1<i>H</i>-1,2, 3-triazol-4-yl]-<i>N</i>-isopropyl-<i>N</i>-methyl-3,6-dihydropyridine-1(2<i>H</i>)-carboxamide (FTIDC), is described. FTIDC inhibits, with equal potency, l-glutamate-induced intracellular Ca<sup>2+</sup> mobilization in Chinese hamster ovary cells expressing human, rat, or mouse mGluR1a. The IC<sub>50</sub> value of 5.8 nM for human mGluR1a 6200 mGluR5....
For patients with a major depressive episode, early differential diagnosis of bipolar disorder and subsequent appropriate treatment are critical. This study, conducted in clinical settings Japan, examined episode to investigate the prevalence predictors disorders.A total 448 were interviewed using Mini-International Neuropsychiatric Interview determine presence mood episodes psychiatric comorbidities. The was based on collected information according DSM-IV-TR.Of 114 (25.4%) diagnosed...
A novel series of (2R)-2-[(1R)-3, 3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides was designed and synthesized based on the structure biological profiles an active metabolite 2 our prototype muscarinic M(3) receptor selective antagonist 1, to develop a potent, long-acting, orally for treatment urinary tract disorders, irritable bowel syndrome, respiratory disorders. Investigation containing phenyl or heterocyclic ring as piperidinyl side chain in place 4-methyl-3-pentenyl moiety 15a...
Comorbid anxiety disorders in patients with mood have a negative impact on outcomes, such as persistence of depressive symptoms, deterioration quality life (QoL), increased suicide risk, instability antidepressant treatment, but often go underrecognized clinical practice. To identify features useful for supporting the confirmation comorbid disorders, we investigated prevalence and their associated factors Japanese using data from our previously reported JET-LMBP study.Patients bipolar...
We established monoclonal antibodies (mAbs) against the mouse macrophage galactose/N-acetylgalactosamine-specific lectin (MMGL) that is a 42-kDa calcium-dependent lectin, using solid phase carbohydrate binding assay as novel strategy for screening mAbs. The specificity of six mAbs were investigated by antibody to native or recombinant forms (rML) MMGL, flow cytometry, and immunoprecipitation cell line RAW264.7. Four these strongly inhibited fluorescein 5-isothiocyanate-labeled galactosylated...
The preventive effects of mood stabilizers on recurrence/relapse in bipolar disorders have been investigated mostly I disorder (BPI) patients, with limited reports II (BPII) patients. Here, we conducted an explorative data analysis to investigate whether the effect lamotrigine recurrence /relapse BPII is better than BPI.Data from Japanese patients a diagnosis BPI or according DSM-IV-TR were analyzed open-label, noninterventional, naturalistic, prospective postmarketing surveillance study...
Abstract Introduction Daprodustat is an approved treatment for anemia of chronic kidney disease (CKD) in Japan. Methods This post hoc analysis evaluated pooled safety data daprodustat from 3 phase Japanese studies dialysis‐dependent and nondialysis patients with CKD. Results Median drug exposure duration was 365 days both ( N = 369) injectable erythropoiesis‐stimulating agent (ESA, 285). The incidence per 100 patient‐years on‐therapy adverse events (AEs) 363.1 306.4 the ESA groups,...
Synthesis and structure–activity relationship of a new class muscarinic M3 selective antagonists were described. In the course searching for antagonist with structure distinct from those 2-(4,4-difluorocyclopentyl)-2-phenylacetamide derivatives, we identified thiazole-4-carboxamide derivative (1) as lead compound in our in-house chemical collection. Since this showed relatively low binding affinity (Ki=140 nM) receptors human assays, tried to improve its potency selectivity over M1 M2 by...
Identification of a novel class potent and highly selective M3 muscarinic antagonists is described. First, the structure−activity relationship in cationic amine core our previously reported triphenylpropionamide was explored by small diamine library constructed solid phase. This led to identification with piperidine pharmacophore significantly improved subtype selectivity from class. Successive modification on terminal part newly identified gave 14a as antagonist that had >100-fold versus...