Proteasome Inhibitors - Biotech, Pharma and Life Science Channel
The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. Due to the importance of the proteasome in cellular functions, inhibition or activation of the proteasome could become a useful therapeutic strategy for a variety of diseases.
Many proteasome inhibitors have been identified and can be classified into two groups according to their source: chemically synthesized small molecules and compounds derived from natural products. A successful example of development of a proteasome inhibitor as a clinically useful drug is the peptide boronate, PS341 (Bortezomib). The drug was approved for the treatment of multiple myeloma. In contrast to proteasome inhibitors, small molecules that can activate or enhance proteasome activity are rare and are not well studied. Despite the commercial success of Velcade, the pipeline of novel proteasome inhibitors is not overcrowded which might indicate the difficulties in identifying new clinical candidates, but also offers a competitive advantage.
News Articles
SEATTLE, June 17, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced results from a pooled analysis of data from completed Phase 1 and 2 studies of pacriti...
Enanta Pharmaceuticals to Present at the Wells Fargo Securities 2013 Healthcare Conference
Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field,...
The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has concluded that the effects of the painkiller diclofenac on the heart and circulation when given systemically (b...
NORCROSS, Ga., June 12, 2013 /PRNewswire-USNewswire/ -- Galectin Therapeutics (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today an...
rEVO Biologics, an LFB Company, announced today that it has completed the treatment and follow up phase of a key dose ranging study of LR769, a novel recombinant form of hu...
The Angeles Clinic and Research Institute presented groundbreaking new data on “Clinical Activity, Safety and Biomarkers of MPDL3280A, an Engineered PD-L1 Antibody in Pat...
Proteostasis Therapeutics, Inc., a company developing novel therapeutics that regulate protein homeostasis to improve outcomes for patients with neurodegenerative and orphan disea...
Turkey's Hepatitis C Virus Drug Market Will More Than Triple by 2017
BURLINGTON, Mass., June 4, 2013 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, forecasts that, from 2012 to 2017,...
LAUSANNE, Switzerland, June 4, 2013 /PRNewswire/ -- Debiopharm Group™ (Debiopharm), a Swiss-based global biopharmaceutical group of companies with a focus on the development of prescrip...
Takeda Pharmaceutical Company Limited (TSE:4502) today reported results from a Phase 1 study evaluating the safety, tolerability, and maximum tolerated dose (MTD) of MLN9708, the...
Events
Diabetes: Secondary Complications, Regulation and Innovation Conference
SMi is very proud to present our 11th conference focusing on Diabetes and metabolic disorders taking place on 1st and 2nd Oct 2013, London.
Companies
The Angeles Clinic and Research Institute
âThe Angeles Clinic and Research Instituteâs mission is to advance cancer care through groundbreaking research and delivering innovative therapeutic options to al...
DOV is a biopharmaceutical company historically focused on the development of novel product candidates for disorders of the central nervous system. DOV has previously funded drug development and disco...
Onconova, based in Newtown, PA and Lawrenceville, NJ, discovers and develops novel patent- protected small molecule therapeutic agents for cancer, radiation protection and hematol...
Enanta Phatmaceuticals ARE A RESEARCH AND DEVELOPMENT-FOCUSED BIOTECHNOLOGY COMPANY that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in t...
NeurAxon, Inc. (www.neuraxon.com) discovers and develops next-generation pain therapeutics focused on its first-in-class selective inhibitors of neuronal nitric oxide synthase...
Founded in 2001, AB Science is a pharmaceutical company specialising in the research, development and commercialisation of protein kinase inhibitors (PKIs), a new class of targete...
Sagene Pharmaceuticals is a biopharmaceutical company developing novel applications for combinations of FDA-approved drugs to treat diseases associated with aging. Sagene h...
Tensha Therapeutics is developing small molecule bromodomain inhibitors, a new class of epigenetic modulators of gene expression, to treat cancer and other serious disorders. The...
Genkyotex is developing first in class, small molecule therapeutics that specifically and selectively inhibit the NOX family of enzymes. Using a unique screening platform, Genkyot...
Millennium Dental Technologies, Inc.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust cl...
Clinical Trials
The purpose of this research study is to: 1) Determine the highest dose of the drug vorinostat that can be given safely in combination with carboplatin and gemcitabine and 2) determine how...
Pilot Trial to Assess Effect of CNI Conversion of Efalizumab on T Reg Cells
The purpose of this pilot trial is to determine whether a conversion from calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) to a regimen consisting of efalizumab and sirolimus i...
89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition
HSP90 inhibition is a potentially new targeted drug modality in the treatment of HER2 positive, trastuzumab refractory breast cancer. Little is known about the pharmacodynamics of HSP90 in...
RATIONALE: Aromatase inhibitors, such as letrozole, prevent the formation of estradiol, a female hormone. Giving letrozole together with goserelin, leuprolide, or surgery may be an effecti...
Imatinib Mesylate in Combination With Docetaxel for Advanced, Platinum-Refractory Ovarian Cancer
Imatinib mesylate is an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular...
A Study Of Nasopharyngeal Carcinoma (NPC) Treated With Celecoxib And ZD1839
EGFR and COX-2 are involved in tumorigenesis, angiogenesis and metastases and are frequently over expressed in NPC.COX-2 and EGFR inhibitors are active in NPC.There is synergistic action b...
The Effects of Anabolic Steroids and Protease Inhibitors on People Living With HIV/AIDS
The main aim of the study is to investigate the combined effects of using anabolic steroids and protease inhibitors on fat metabolism and body composition of People Living with HIV/AIDS....
Statins in Proteinuric Nephropathies
End stage renal disease (ESRD) is rapidly growing worldwide. Patients with ESRD have increased morbidity and mortality mostly because of a dramatic excess of cardiovascular disease. Thus,...
Second Line Therapy for the Cure of Helicobacter Pylori (H. Pylori) Infection
Proton pump inhibitors (PPIs) are mainly metabolized in the liver by CYP2C19, one of the cytochrome P450 isoenzymes, which shows a genetic polymorphism associated with enzyme activities. T...
Celebrex With Preoperative Chemoradiation - Rectal Cancer
Colorectal carcinoma is the third most common cause of death from cancer. Approximately, 30% of colorectal carcinomas involve the rectum. Optimizing local control in the pelvis while reduc...
PubMed Articles
Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors.
The majority of human cancers harbour mutations promoting activation of the Akt protein kinase, and Akt inhibitors are being evaluated in clinical trials. An important question concerns the understand...
Engagement of NKG2D and DNAX accessory molecule-1 (DNAM-1) receptors on lymphocytes plays an important role for anticancer response and represents an interesting therapeutic target for pharmacological...
Potent, reversible inhibition of the cytochrome P450 CYP2C9 isoform was observed in a series of urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. This unwanted property was su...
A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was...
1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved t...
Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1).
Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is current...
Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening.
Through structure-based virtual screening, some dozen of benzene sulfonamides with novel scaffolds are identified as potent inhibitors against carbonic anhydrase (CA) IX with IC50 values ranging from...
The synthesis and structure-activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon ce...
Benzobisthiazole derivatives were identified as novel helicase inhibitors through high throughput screening against purified Staphylococcus aureus (Sa) and Bacillus anthracis (Ba) replicative helicase...
Caffeic acid derivatives: A new type of influenza neuraminidase inhibitors.
Recently, many natural products, especially some plant-derived polyphenols have been found to exert antiviral effects against influenza virus and show inhibitory activities on neuraminidases (NAs). In...
Videos
Found in Translation: The Tale of the Cancer Drug Bortezomib (Velcade)
The story of the proteasome inhibitor bortezomib, or Velcade, ended happily, if not where anyone expected, when a collaborative effort to reverse muscle wast...
Medical and Biotech [MESH] Definitions
Taxodium
A plant genus of the family TAXODIACEAE. Members contain taxodione and taxodone, which are diterpenoid quinone methide tumor inhibitors.
Huperzia
A plant genus of the family LYCOPODIACEAE. Members contain huperzine, one of the CHOLINESTERASE INHIBITORS.
Angiostatins
Circulating 38-kDa proteins that are internal peptide fragments of PLASMINOGEN. The name derives from the fact that they are potent ANGIOGENESIS INHIBITORS. Angiostatins contain four KRINGLE DOMAINS which are associated with their potent angiostatic activity.
Pregnancy-associated Alpha 2-macroglobulins
Large (>160 kDa) glycoproteins with electrophoretic mobility of ALPHA-GLOBULINS, found in high concentration in the plasma of pregnant women but also in a number of species including mouse, rat, and others (ALPHA-MACROGLOBULINS). In humans, they are always present in the circulation and are nonspecific inhibitors of PROTEINASES, similar to COMPLEMENT PROTEINS (C3; C4; C5).
Proteasome Endopeptidase Complex
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
