A5101604215- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Hemophilia Treatment and Research
- Diabetes Treatment and Management
- Diagnosis and treatment of tuberculosis
- Blood Coagulation and Thrombosis Mechanisms
- Metabolism, Diabetes, and Cancer
- Quinazolinone synthesis and applications
- Pancreatic function and diabetes
- Click Chemistry and Applications
- Pneumonia and Respiratory Infections
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- Intracerebral and Subarachnoid Hemorrhage Research
- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- Chronic Myeloid Leukemia Treatments
- Animal testing and alternatives
- HIV/AIDS drug development and treatment
- Acute Ischemic Stroke Management
- Chemical Synthesis and Analysis
- Antibiotics Pharmacokinetics and Efficacy
- Biotin and Related Studies
- Biopolymer Synthesis and Applications
Pfizer (United States)
2010-2023
Daping Hospital
2010
Army Medical University
2010
Johns Hopkins Medicine
2008
Johns Hopkins University
2008
A pharmacological approach to inhibition of cyclin-dependent kinases 4 and 6 (Cdk4/6) using highly selective small molecule inhibitors has the potential provide novel cancer therapies for clinical use. Achieving high levels selectivity Cdk4/6, versus other ATP-dependent kinases, presents a significant challenge. The pyrido[2,3-d]pyrimidin-7-one template provides an effective platform broad cross-section including Cdks. It is now demonstrated that modification pyrido[2,3-d]pyrimidin-7-ones...
Oxazolidinone antibiotics have activity against Mycobacterium tuberculosis. Linezolid, the only marketed oxazolidinone, has been used off-label in combination regimens to treat multidrug-resistant tuberculosis, but its precise contribution efficacy of such combinations is unclear. Another PNU-100480, demonstrated more potent vitro and a murine model In this study, we compared pharmacokinetics antituberculosis activities these two oxazolidinones over range doses found that linezolid limited...
As the need for novel antibiotic classes to combat bacterial drug resistance increases, paucity of leads resulting from target-based antibacterial screening pharmaceutical compound libraries is major concern. One explanation this lack success that efforts have not leveraged eukaryotic bias more extensive chemistry targeting gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on target space resembling these targets, we used whole-cell identify...
Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid its first patients.Sputum smear positive patients were randomly assigned 600 mg BID (N = 25) or 1200 QD 25), 4-drug therapy 9) for 14 days treatment. Effects on mycobacterial burden sputum (early EBA) monitored as...
Compound 4 (PF-04971729) belongs to a new class of potent and selective sodium-dependent glucose cotransporter 2 inhibitors incorporating unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. In this paper we present the design, synthesis, preclinical evaluation, human dose predictions related 4. This compound demonstrated robust urinary excretion in rats an excellent safety profile. It is currently phase clinical trials being evaluated for treatment type diabetes.
We recently reported strong bactericidal activity of the oxazolidinone PNU-100480 and its ability to increase initial effect various combinations first-line tuberculosis drugs moxifloxacin in a murine model.To investigate whether addition standard regimen rifampin, isoniazid, pyrazinamide could shorten duration treatment necessary prevent relapse after discontinuation.Following aerosol infection with Mycobacterium H37Rv 13-day incubation period, control mice were treated while test received...
Tuberculosis is a serious global health threat for which new treatments are urgently needed. This study examined the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses oxazolidinone PNU-100480 in healthy volunteers, using biomarkers safety efficacy. Subjects were randomly assigned to or placebo (4:1) at schedules 100, 300, 600 mg twice daily 1,200 14 days schedule 28 pyrazinamide was added on 27 28. A sixth cohort given linezolid 300 4 days. Signs,...
Inhibition of DGAT2 reduces steatosis, inflammation, and fibrosis in rodent models NASH liver fat clinical testing.
Structure–activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined a series quinazoline- pyrido[3,4-d]pyrimidine-based analogues the irreversible pan-erbB inhibitor, canertinib. Cyclic amine bearing crotonamides to provide rapid cellular erbB1 autophosphorylation good metabolic stability in liver microsome hepatocyte assays. The influence 4-anilino substitution on inhibitory potency was investigated. Several anilines identified as providing potent, reversible...
ABSTRACT Sutezolid (PNU-100480 [U-480]) is an oxazolidinone antimicrobial being developed for the treatment of tuberculosis. An active sulfoxide metabolite (PNU-101603 [U-603]), which reaches concentrations in plasma several times those parent, has been reported to drive killing extracellular Mycobacterium tuberculosis by sutezolid hollow-fiber culture. However, relative contributions parent and against intracellular M. vivo are not fully understood. The relationships between U-480 U-603...
Summary A phase 1b/2, three‐month study of marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), was conducted in participants with haemophilia or B, without inhibitors. Participants assigned to four cohorts received escalating weekly doses based on status (without inhibitors: 300 mg, single 300‐mg loading dose subsequent 150‐mg doses, 450 mg; mg). Safety outcomes were treatment‐emergent adverse events (TEAEs), injection site reactions, clinical and...
Oxazolidinones possessing a C-5 carboxamide functionality (reverse amides) represent new series of compounds that block bacterial protein synthesis. These reverse amides also exhibited less potency against monoamine oxidase (MAO) enzymes and thus possess potential for the side effects associated with MAO inhibition. The title compound (14) showed reduced in vivo myelotoxicity compared to linezolid 14-day safety study rats, potent efficacy murine systemic infection models, excellent...
Background and Purpose: This study aimed to determine the maximum tolerated dose evaluate overall safety tolerability of single doses PF-05230907 in subjects with acute intracerebral hemorrhage. Methods: Individuals presenting hemorrhage were enrolled a phase 1, multicenter, open-label clinical trial. A Bayesian modified continual reassessment method design based on treatment-emergent thromboembolic or ischemic events was adopted. Sequential dosing, an external data monitoring committee,...
Abstract Tissue factor pathway inhibitor (TFPI) is an endogenous of the extrinsic coagulation pathway. In patients with hemophilia A or B, inhibition TFPI alternative therapeutic approach that augments Marstacimab investigational fully human monoclonal antibody binds and neutralizes being evaluated as a prophylactic treatment to prevent reduce frequency bleeding episodes in severe without inhibitors (antibodies against factors). However, efficacy, safety, pharmacokinetics marstacimab may be...
What is this summary about? This a of the results from two clinical studies treatment for men with severe hemophilia A or B. The were published in British Journal Haematology. People either have low amounts clotting factors are missing certain their blood. severity found out by blood test. There medicines that people can take to replace factor. However, sometimes body thinks factor used treat foreign substance and produces antibodies destroy it (called inhibitors) which may slow down stop...