A5069846611- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Cancer therapeutics and mechanisms
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Bacteriophages and microbial interactions
- Cancer Treatment and Pharmacology
- Microbial Natural Products and Biosynthesis
- Microtubule and mitosis dynamics
- Antimicrobial Resistance in Staphylococcus
- Kruppel-like factors research
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
- Uterine Myomas and Treatments
- Bacterial biofilms and quorum sensing
- Antimicrobial Peptides and Activities
- Bacterial Infections and Vaccines
- Viral gastroenteritis research and epidemiology
- TGF-β signaling in diseases
- Mechanisms of cancer metastasis
- Cancer Research and Treatments
- Lymphoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Viral-associated cancers and disorders
PTC Therapeutics (United States)
2007-2022
Gause Institute of New Antibiotics Russian Academy of Medical Sciences
2002
University of Debrecen
2002
Hungarian Academy of Sciences
2002
Advanced Pharma
2000-2001
Princeton University
2000
Walter Reed Army Institute of Research
1995-1997
OpenCell Technologies (United States)
1997
Wright State University
1990-1991
Direct inoculation of DNA, in the form purified bacterial plasmids that are unable to replicate mammalian cells but able direct cell synthesis foreign proteins, is being explored as an approach vaccine development. Here, a highly attenuated Shigella vector invaded and delivered such into cytoplasm cells, subsequent production functional protein was measured. Because this designed deliver DNA colonic mucosa, method potential basis for oral other mucosal immunization gene therapy strategies.
Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria involves multiple enzymes under strict temporal spatial regulation. We used set of small inhibit the transglycosylation step peptidoglycan to discover genes help regulate this process. identified gene responsible susceptibility Escherichia coli cells killing by glycolipid derivatives vancomycin, thus...
Disease recurrence is the major problem in treatment of acute myeloid leukemia (AML). Relapse driven by stem cells, a chemoresistant subpopulation capable re-establishing disease. Patients with p53 mutant AML are at an extremely high risk relapse. B-cell-specific Moloney murine virus integration site 1 (BMI-1) required for self-renewal and maintenance cells. Here we studied effects novel small molecule inhibitor BMI-1, PTC596, Treatment PTC596 reduced MCL-1 expression triggered several...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA New Mechanism of Action Proposed for RamoplaninMei-Chu Lo, Hongbin Men, Arthur Branstrom, Jeremiah Helm, Nan Yao, Robert Goldman, and Suzanne WalkerView Author Information Department Biology, Incara Pharmaceuticals Cranbury, Jersey 08512 Chemistry Princeton Materials Institute University, Princeton, 08544 Cite this: J. Am. Chem. Soc. 2000, 122, 14, 3540–3541Publication Date (Web):March 23, 2000Publication History Received18 January...
Moenomycin is a natural product glycolipid that inhibits the growth of broad spectrum Gram-positive bacteria. In Escherichia coli, moenomycin peptidoglycan synthesis at transglycosylation stage, causes accumulation cell-wall intermediates, and leads to lysis cell death. However, unlike Esc. where 5-6 log units killing are observed, 0-2 occurred when bacteria were treated with similar multiples MIC. addition, bulk in intact cells was resistant effects moenomycin. contrast, synthetic...
Klebsiella pneumoniae is a Gram-negative bacterium that responsible for range of common infections, including pulmonary pneumonia, bloodstream infections and meningitis. Certain strains have become highly resistant to antibiotics. Despite the vast amount research carried out on this class bacteria, molecular structure its topoisomerase IV, type II essential catalysing chromosomal segregation, had remained unknown. In paper, DNA-cleavage complex reported at 3.35 Å resolution. The comprised...
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that broadly chemoresistant, due in part to biophysical properties of tumor stroma, which serves as barrier drug delivery for most classical chemotherapeutic drugs. The goal this work evaluate the preclinical efficacy and mechanisms PTC596, novel agent with potent anticancer vitro desirable pharmacologic vivo. Experimental Design: We assessed pharmacology, mechanism, PTC596 combination standards care, using multiple...
ADVERTISEMENT RETURN TO ISSUELetterNEXTDiscovery of Novel Disaccharide Antibacterial Agents Using a Combinatorial Library ApproachMichael J. Sofia, Nigel Allanson, Nicole T. Hatzenbuhler, Rakesh Jain, Ramesh Kakarla, Natan Kogan, Rui Liang, Dashan Liu, Domingos Silva, Huiming Wang, David Gange, Jan Anderson, Anna Chen, Feng Chi, Richard Dulina, Buwen Huang, Muthoni Kamau, Chunguang Eugene Baizman, Arthur Branstrom, Neil Bristol, Robert Goldman, Kiho Han, Clifford Longley, Sunita Midha, and...
Novel glycopeptide analogs are known that have activity on vancomycin resistant enterococci despite the fact primary site for drug interaction, D-ala-D-ala, is replaced with D-ala-D-lactate. The mechanism of action these compounds may involve dimerization and/or membrane binding, thus enhancing interaction D-ala-D-lactate, or a direct transglycosylase enzymes involved in peptidoglycan polymerization. We evaluated ability (V), desleucyl-vancomycin (desleucyl-V), chlorobiphenyl-vancomycin...
Antibiotic-resistant Neisseria gonorrhoeae (Ng ) are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum activity against Ng including MDR isolates. By selecting organisms the inhibitors sequencing their genomes, we new therapeutic target, class Ia ribonucleotide reductase (RNR). Resistance mutations in map N-terminal cone domain α subunit,...
Des-(N-methyl-d-leucyl)eremomycin was obtained by Edman degradation of eremomycin. Derivatives with a hydrophobic substituent at the exterior molecule were then synthesized, and their antibacterial activities compared similar derivatives Comparison eremomycin containing n-decyl or p-(p-chlorophenyl)benzyl in eremosamine moiety (N') p-(p-chlorophenyl)benzylamides possessing damaged peptide core (a defective binding pocket) showed that compounds both types are almost equally active against...
Abstract PTC596 is a novel, orally bioavailable, small‐molecule tubulin‐binding agent that reduces B‐cell–specific Moloney murine leukemia virus insertion site 1 activity and being developed for the treatment of solid tumors. A phase 1, open‐label, multiple‐ascending‐dose study was conducted to evaluate pharmacokinetics safety drug in subjects with advanced administered biweekly based on body weight. Dose escalation followed modified 3 + scheme using doses 0.65, 1.3, 2.6, 5.2, 7.0, 10.4...
PTC596 is an investigational small-molecule tubulin-binding agent. Unlike other agents, orally bioavailable and not a P-glycoprotein substrate. So as to characterize position the molecule for optimal clinical development, interactions of with tubulin using crystallography, its spectrum preclinical
Blocking the pyrimidine nucleotide de novo synthesis pathway by inhibiting dihydroorotate dehydrogenase (DHODH) results in cell cycle arrest and/or differentiation of rapidly proliferating cells including activated lymphocytes, cancer cells, or virally infected cells. Emvododstat (PTC299) is an orally bioavailable small molecule that inhibits DHODH. We evaluated potential for emvododstat to inhibit progression acute myeloid leukemia (AML) using several vitro and vivo models disease. Broad...
The rational design of novel antibiotics for bacteria involves the identification inhibitors enzymes involved in essential biochemical pathways cells. In this study, cloning, expression, purification, crystallization and structure enzyme peptidyl-tRNA hydrolase from Francisella tularensis, causative agent tularemia, was performed. F. tularensis is comparable to those other bacterial hydrolases, with most residues active site conserved amongst family. resultant reagents, structural data...
Despite the development of novel Bruton tyrosine kinase inhibitor ibrutinib, mantle cell lymphoma (MCL) remains an incurable B-cell non-Hodgkin lymphoma. BMI-1 is required for self-renewal and maintenance MCL-initiating stem cells. Upregulation has been reported in MCL patients, especially those with refractory/relapsed disease. We studied effects a small-molecule selective BMI1 expression, PTC596, Eight lines patient-derived samples were exposed to PTC596. PTC596 induced mitochondrial...
With rising incidence rates, endometrial cancer is one of the most common gynecologic malignancies in United States. Although surgery provides significant survival benefit to early-stage patients, those with advanced or recurrent metastatic disease have a dismal prognosis. Limited treatment options include chemotherapy and radiotherapy. Hence, there compelling need for developing molecularly targeted therapy. Here, we show that polycomb ring finger protein BMI1, also known as stem cell...
There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) bacterial infections, particularly those caused by Gram-negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors type II topoisomerases active against MDR bacteria. Herein, we report on the discovery and structure–activity relationships series fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antibacterial activity...
An in situ transglycosylase assay has been developed using endogenously synthesized lipid II. The involves the preferential synthesis and accumulation of II a reaction mixture containing cell wall membrane material isolated from Escherichia coli, exogenously supplied UDP-MurNAc-pentapeptide, radiolabeled UDP-GlcNAc. In presence Triton X-100, product formed is almost exclusively II, while subsequent formation peptidoglycan inhibited. Removal detergent resulted (25% incorporation material)...