A5103016180- Pituitary Gland Disorders and Treatments
- Pharmacogenetics and Drug Metabolism
- Biochemical Analysis and Sensing Techniques
- Growth Hormone and Insulin-like Growth Factors
- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Neuroendocrine Tumor Research Advances
- Adrenal and Paraganglionic Tumors
- Adipose Tissue and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Pharmacological Receptor Mechanisms and Effects
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Adrenal Hormones and Disorders
- Neuroscience and Neuropharmacology Research
- Hypothalamic control of reproductive hormones
- Drug Transport and Resistance Mechanisms
- Alcohol Consumption and Health Effects
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pancreatic function and diabetes
- Diet and metabolism studies
- Allergic Rhinitis and Sensitization
- Asthma and respiratory diseases
- Estrogen and related hormone effects
- Natural Compound Pharmacology Studies
Crinetics Pharmaceuticals (United States)
2017-2025
Crozer-Keystone Health System
2024
Sanjivani Super Speciality Hospitals
2019-2020
Neurocrine Biosciences (United States)
2005-2017
Almirall (Spain)
2009
PRA Health Sciences
2009
Sekisui XenoTech (United States)
1999
W.E. Upjohn Institute for Employment Research
1999
University of Kansas
1993-1998
University of Kansas Medical Center
1996-1998
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine other monoamines from neuronal vesicles into synapse. Valbenazine (NBI-98854), a novel compound selectively inhibits VMAT2, approved for treatment tardive dyskinesia. converted to two significant circulating metabolites in vivo, namely, (+)-<i>α</i>-dihydrotetrabenazine (R,R,R-HTBZ) mono-oxy metabolite, NBI-136110. Radioligand-binding studies were...
Pregnane X receptor (PXR) and constitutive androstane (CAR) are key regulators of xenobiotic-inducible cytochrome P450 gene expression. Whereas much is known about their role in regulating drug metabolism, little regarding transport vivo. Wild-type mice lacking PXR (PXR-KO) were used to examine the inducible expression two transporter genes, Oatp2 (Slc21a5) Mrp3 (Abcc3), liver following treatment with selective CAR activators. Selective activation or induced wild-type but not PXR-KO mice....
The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus this optimization was to improve the CYP3A4 inhibition liability these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric sodium salt, 10b (elagolix), identified and...
Castleman's disease (CD) is characterized by lymph node enlargement due to hyperplasia of abnormal lymphoid follicles and paracortical lymphocytic hyaline vascular (HV) stroma or plasmacytosis (PC). The in CD show involuted germinal centers prominent mantle zone lymphocytes. Ninety-seven cases clinically suspected be were analyzed according conventional histologic criteria established Castleman Keller for diagnosis. Twenty-two excluded as nonspecific (12); Hodgkin's non-Hodgkin's lymphoma...
Analogues of the known H(1)-antihistamine R-dimethindene were profiled as potential agents for treatment insomnia. Several highly selective compounds efficacious in rodent sleep models. On basis overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable evaluation night time dosing. Compound did not show an vivo cardiovascular effect from weak hERG channel inhibition.
There are five situations in a women's life during which hormone fluctuations make them more susceptible to oral health problems - puberty, at certain points the monthly menstrual cycle, when using birth control pills, pregnancy, and menopause. The present study aimed evaluating effect of menstruation, pregnancy menopause on salivary flow rate, pH gustatory function.
Abstract Context Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly. Objective This work aimed to evaluate change insulin-like growth factor I (IGF-I) levels patients switched from octreotide long-acting release or lanreotide depot monotherapy paltusotine. Methods A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted...
In the present study, we evaluated inducibility of cytochrome P-450 (CYP) CYP1A, CYP2B, CYP3A, and CYP4A by beta-naphthoflavone, phenobarbital, dexamethasone, clofibric acid, respectively, in primary hepatocyte cultures prepared from both fresh cryopreserved rat hepatocytes. Rat hepatocytes were successfully thawed cultured after cryopreservation liquid nitrogen for up to 1 month. Percentage total recovery, viable cell final viability cells 68%, 72%, 85%, respectively. Regardless whether...
Abstract Purpose Evaluate the pharmacodynamics, pharmacokinetics, and safety of paltusotine, an orally bioavailable, nonpeptide, somatostatin receptor subtype 2 (SST2) agonist being developed for treatment acromegaly neuroendocrine tumors. Methods A randomized, double-blind, placebo-controlled, single center, multiple ascending dose phase 1 study was conducted in healthy male volunteers who received (i) single-dose oral paltusotine 1.25, 2.5, 5, 10, 20 mg (solution); 40 60 (capsules) or (ii)...
Paltusotine is a novel, nonpeptide, selective somatostatin receptor 2 agonist in development for the treatment of acromegaly and carcinoid syndrome. This study investigated mass balance, routes excretion, absolute bioavailability metabolite profile orally administered paltusotine. In Part A two-part, phase 1 study, single dose (oral solution) 20 mg paltusotine containing approximately 3.0 MBq (80 μCi) 14C-labelled was to six healthy male participants evaluate balance B, followed 90 min later...
To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg).Five antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 diphenhydramine, were administered to as 0.1-mg i.v. dose. Blood samples collected up 48 h, parent compound plasma extract was quantified by high-performance liquid chromatography accelerator mass spectroscopy.The median clearance (CL), apparent volume distribution (V(d)) terminal...
The aim of this study was to determine the in vitro and vivo effects several prototypical inducers, namely beta-naphthoflavone, 3-methylcholanthrene, phenobarbital, isoniazid, rifampin, clofibric acid, on expression cytochrome P450 (P450) enzymes beagle dogs. For induction study, primary cultures dog hepatocytes were treated with enzyme inducers for 3 days, after which microsomes prepared analyzed activities. male female dogs 4 days (with exception given 14 days), livers removed microsomal...
The discovery of a novel 4-(4-aminopiperidinyl)-3,6-diarylquinoline series potent SST2 agonists is described. This class molecules exhibit excellent selectivity over SST1, SST3, SST4, and SST5 receptors. compound 3-[4-(4-aminopiperidin-1-yl)-3-(3,5-difluorophenyl)quinolin-6-yl]-2-hydroxybenzonitrile (22, paltusotine, formerly known as CRN00808) showed no direct inhibition major cytochrome P450 enzymes or the hERG ion channel had sufficient exposure in rats dogs upon oral dosing. In...
Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, good oral bioavailabilty rats. The thiophene analogue exhibited low iv clearance, long half-life, brain penetration. In obese rats, thienopyridazinone demonstrated dose-dependent reduction feeding body weight with doses between 1 10 mg kg-1.
In the present article, we report on a strategy to improve physical properties of series small molecule human adenosine 2A (hA2A) antagonists. One aromatic rings typical this antagonists is replaced with aliphatic groups, aim disrupting crystal packing lower melting point and in turn solubility. Herein, describe SAR new water-soluble 2,4,6-trisubstituted pyrimidines where R1 an heterocycle, R2 short-chain alkyl amide, R3 heterocyclic substituent amino substituent. This approach significantly...
Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with wide range of commercial applications. The present study was designed to investigate the effects D5 on expression and activity selected rat hepatic phase I II metabolizing enzymes. Female Fischer-344 rats were exposed 160 ppm vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in relative abundance microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, CYP4A), epoxide hydrolase, UDP-glucuronosyltransferase...