We continue to present recent international patent applications that tap into the universe of pharmacologically active compounds – in development, marketed, proprietary, generic, successful or failed – to find new medical uses for molecules that are already known. As this database grows, its areas of overlap with our Discontinued Drug Database – which goes back to the early 1990s – develop in number, size, and internal structure. Stay with us on this exciting journey, which is just beginning! – And please contact us – as per below – for any inquiries you may have.
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An Adjunct Drug for Parkinson’s Disease Prevents Obesity
The catechol-O-methyltransferase (COMT) inhibitor, entacapone(Novartis’ and Orion’s Comtess®/Comtan®; also a component in Stalevo®) slows the enzymatic degradation of co-administered L-dopa in patients with Parkinson’s disease. Like the closely related tolcapone it is also a potent inhibitor of α-synuclein and β-amyloid oligomerization and fibrillogenesis (J Biol Chem 2010; 285(20): 14941-54, here), an action which it shares with many other antiparkinsonian agents (J Neurosci Res. 2013; 91(10): 1371-81, here). This might be of additional help in Parkinson’s disease and makes it a potential repurposing candiate for Alzheimer’s disease. WO/2014/082544(Natl. Inst. of Biol. Sciences [CN]; June 5, 2014) says entacapone has another, completely different action – it is an inhibitor of of the fat mass and obesity-associated gene product (FTO; an α-ketoglutarate and iron(II)-dependent nucleic acid demethylase; see Endokrynol Pol. 2014; 65(3): 224-31, here), and hence a potential obesity treatment. The adipose and hepatic tissues of Wistar rats treated with entacapone while on a high-fat diet showed dramatic changes comparing to control group, with reduced size of adipose cells and reduced liver steatosis. The difference in LDL-cholesterol was most dramatic (-41%), equaling that of statins.
Marimastat for Polycystic Liver Disease
British Biotech plc, the UK life science industry’s highflyer around the millennium, had most of its hopes riding on marimastat, an orally active broad spectrum inhibitor of matrix metalloproteinases that the company developed to prevent cancer metastasis. Rights had already been licensed to Schering-Plough and Tanabe Seiyaku but Phase III trials failed. WO/2014/083229(Basque Regional Gov. [ES]; June 5, 2014) gives the compound new hope in polycystic liver diseases (Orphanet J Rare Dis. 2014; 9: 69; here), which can manifest in isolation or in association with polycystic kidney disease. This is on-target repurposing: marimastat blocks the metalloproteolytic hyperactivity of the polycystic cholangiocytes. (See the companion peer review paper in Gut 2014 Jan 16, here.) At present, the cysts are treated conservatively, sometimes with somatostatin analogs.
Peroxisome Proliferator Activated Receptor Delta Agonists for Myocardial Infarction
PPAR agonists (the glitazones) had originally been developed as antidiabetics, but their pleiotropic nature soon became apparent. PPARs play a key role in metabolic regulatory processes and gene regulation of cellular metabolism, particularly in the cardiovascular system. That several, chemically distinct ligands of PPAR-γ(and to a lesser degree, PPAR-α) reduce tissue necrosis after acute myocardial infarction has been known for many years (FASEB J. 2002; 16(9): 1027-40, here); also that activation of the PPAR-δreceptor normalizes cardiac substrate metabolism in congestive heart failure (J Cardiovasc Pharmacol. 2007; 50(1): 25-34, here). In WO/2014/084433(Gyeonsang Natl. Univ. [KR]; June 5, 2014) the post-infarction use is extended to PPAR-δ agonists, chosen from GlaxoSmithKline’s Endurobol(GW-501516; first disclosed in WO/2001/00603and claimed for respiratory infections in WO/2013/134626as reviewed by us here), GW-610742, GSK-0660, or GSK-3787.
Antimalarials for Kidney Disease
Artemisinin-based combination therapies are the WHO-recommended first-line treatments of Plasmodium falciparum malaria in all countries with endemic disease. Most recently it was reported that artemisinin might have some anticancer potential (Nat Prod Bioprospect. 2014; 4: 189-196, here). But almost at the same time WO/2014/090306(Queen Mary & Westfield College [GB]; June 19, 2014)claimed utility of artemisinin, artesunate, and other related antimalarials in acute kidney injury (e.g., after coronary artery bypass surgery or hemorrhagic shock) even after its onset, in renal surgery, and in kidney transplantation. Rat data from renal ischemia models seem convincing.