Small Molecule Inhibitor of Cholesterol Biosynthesis and Venous Angiogenesis
Inhibits the HMGCR pathway through a different mechanism than statins. Identifies probes specific to a phenotype of interest and thus does not require prior target identification and validation.
Reduction of cellular cholesterol. Inhibition of tumor growth through repression of angiogenesis.
Researchers at UCLA have identified a non-statin small molecule, aplexone, which reduces cellular cholesterol levels more effectively than atorvastatin (Lipitor). Like statins, aplexone inhibits the HMG-CoA reductase (HMGCR) pathway, but does not contain the same motif and thus likely inhibits the pathway through a different mechanism. Aplexone shows lower toxicity and a substantially lower molecular weight than atorvastatin. In addition to its role in inhibiting cholesterol biosynthesis, aplexone was found to repress angiogenesis and may inhibit tumor growth. This molecule can be further developed as both a cholesterol-lowering drug and a cancer chemotherapeutic.
Patent Number: US20130289073A1
Application Number: US13979566A
Inventor: Kwon, Ohyun | Chen, Jau-Nian
Priority Date: 14 Jan 2011
Priority Number: US20130289073A1
Application Date: 12 Jul 2013
Publication Date: 31 Oct 2013
IPC Current: A61K00314418 | A61K00314436 | A61K004506 | C07D021196 | C07D040904
US Class: 514336 | 435375 | 506010 | 514355 | 546315
Assignee Applicant: The Regents of the University of California
Title: CHEMICAL INHIBITORS OF CHOLESTEROL BIOSYNTHESIS AND VENOUS ANGIOGENESIS
Usefulness: CHEMICAL INHIBITORS OF CHOLESTEROL BIOSYNTHESIS AND VENOUS ANGIOGENESIS
Summary: (I) are useful for inhibiting angiogenesis, or for lowing cellular cholesterol levels in a subject (human); treating, inhibiting or delaying the onset or progression of an angiogenesis-mediated condition or disease, including cancer and an inflammatory disease in the subject; reducing the amount of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the subject; and inhibiting angiogenesis or reducing cholesterol in an in vitro system containing (I), cell extract, cell or organ (all claimed). Test details are described but no results given.
Novelty: New substituted sulfonyl benzene compounds, that are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, used e.g. treating, inhibiting or delaying progression of angiogenesis-mediated condition e.g. cancer in a subject (human)
診斷/治療
癌症/腫瘤
9084782
State Of Development The cholesterol-lowering and antiangiogenic properties of aplexone have been tested in vivo in an embryonic zebrafish model. Background Statins are a class of small molecule drugs used for lowering blood cholesterol levels and preventing cardiovascular disease. Atorvastatin, sold by Pfizer under the trade name Lipitor, is the best-selling drug in history, with sales exceeding $11 billion in 2010. This figure is expected to drop dramatically with U.S. patent expiry and the availability of a generic version in November 2011. All statins, including atorvastatin, inhibit HMG-CoA reductase (HMGCR), an enzyme found in liver tissue that plays a key role in cholesterol production. Experimental evidence suggests that this key biochemical pathway also plays an important role in the oncogenic process, and statin administration in vivo has been shown to inhibit tumor growth. However, a number of rare but serious side effects have been attributed to statins, including muscle and liver damage. Researchers are working to identify the next generation of cholesterol-lowering small molecule drugs with greater efficacy and reduced side effects, and to understand and modulate the HMGCR pathway for cancer therapy. Additional Technologies by these Inventors Tech ID/UC Case 22106/2011-417-0 Related Cases 2011-417-0
美國
