Drug Discovery Today
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Angiotensin receptor blockers: a panacea for Marfan syndrome and related disorders?
• Study of Marfan mouse models revealed a key role for TGFβ signaling in the pathogenesis of aortic aneurysm. • Canonical and noncanonical TGFβ signaling play parts in...
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Pharmacokinetics, metabolism and distribution of PEGs and PEGylated proteins: quo vadis?
The pharmacokinetics (PK), metabolism and biodistribution of polyethylene glycol (PEG) in PEGylated proteins are important to understand the increased cellular vacuolation reported in various tissues in animals. The tissue distribution profile of PEGylated proteins and 'metabolic' PEG is guided larg...
Nutraceuticals in joint health: animal models as instrumental tools.
Osteoarthritis (OA) is a degenerative joint disease with no curative treatments. Many studies have begun to demonstrate the efficacy of nutraceuticals for slowing down OA. Animal models are utilized as a compulsory step in demonstrating the protective potential of these compounds on joint health. Ne...
Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches.
Gastrointestinal cancers are asymptomatic in early tumor development, leading to high mortality rates. Peri- or postoperative chemotherapy is a common strategy used to prolong the life expectancy of patients with these diseases. Understanding the molecular mechanisms by which anticancer drugs exert...
The emerging role of speckle-type POZ protein (SPOP) in cancer development.
Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is an E3 ubiquitin ligase adaptor protein that is frequently mutated in prostate and endometrial cancers. All the cancer-associated SPOP mutations reported to date are clustered in the meprin and TRAF (Tumor necrosis factor receptor...
Histamine H4 receptor antagonists for the treatment of inflammatory disorders.
Since its initial discovery by Sir Henry Dale and Patrick Laidlaw in 1910, the biogenic amine histamine has been one of the most widely researched molecules in science. H4R, the newest member of the histamine receptor family, was first identified at the turn of the millennium. Its predominant expres...
How do we measure pathology in PAH (lung and RV) and what does it tell us about the disease.
The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation,...
Modulation of PGC-1α activity as a treatment for metabolic and muscle-related diseases.
Financing drug discovery for orphan diseases.
We demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount...