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Fluorescent Amyloid Binding Agents for Diagnosis of Alzheimer's Disease

技術優勢

Simple synthesis and chemistries amenable to modification and production at large scales. Fluorescence profile optimized for in vivo characterization of amyloid deposits using existing and widely accessible imaging instruments. These probes may be used for the monitoring of disease progression in the development of new therapeutic treatments.

技術應用

Fluorescent probes are compatible with in vivo fluorescence imaging instruments. Generally relevant for the early diagnosis of diseases characterized by amyloid aggregates, such as Alzheimer’s, Parkinson, Huntington disease, and rheumatoid arthritis.

詳細技術說明

A common structural feature of known amyloid-binding agents is an electronically-polarized, extended aromatic system that is inherent to a family of fluorescent probes known as molecular rotors. Features of molecular rotors, which inherently decrease the non-radiative decay rate and increase fluorescence emission upon binding to aggregated beta-amyloids, were incorporated into a general design of novel, amyloid-binding agents.

*Abstract

Amyloids are insoluble fibrous protein aggregates that accumulate in various organs throughout the human body. It has been clinically proven that abnormal accumulation of beta-amyloids in the brain is associated with various neurodegenerative diseases, including Alzheimer disease. Diagnostic biomarkers currently in clinical development are limited to small radio-labeled molecules for detection of amyloidosis through PET or SPECT imaging modes. There remains a pressing need for the design and development of new imaging agents for conclusive early diagnosis of Alzheimer’s disease, ideally through widely accessible detection platforms.

*IP Issue Date

Jan 27, 2015

*Principal Investigation

Name: Emmanuel Theodorakis

Department:

Name: Jerry Yang

Department:

附加資料

Patent Number: US20120302603A1
Application Number: US13515239A
Inventor: Yang, Jerry | Theodorakis, Emmanuel A.
Priority Date: 10 Dec 2009
Priority Number: US20120302603A1
Application Date: 9 Aug 2012
Publication Date: 29 Nov 2012
IPC Current: C07C025543 | A61K0031277 | A61K0031451 | A61P002528 | C07D0295155 | G01N002164 | G01N0033566
US Class: 514319 | 436501 | 514521 | 546205 | 558402 | 558403
Assignee Applicant: The Regents of the University of California
Title: AMYLOID BINDING AGENTS
Usefulness: AMYLOID BINDING AGENTS
Summary: For treating a disease caused by accumulation of amyloids in a subject, for treating Alzheimer's disease, bovine spongiform encephalopathy (BSE), Parkinson's disease, Huntington's disease, Down's Syndrome, dementia with Lewy body, or amyotrophic lateral sclerosis (ALS) (all claimed).
Novelty: New 2-cyano-acrylic acid derivatives useful for treatment of e.g. Alzheimer's disease, bovine spongiform encephalopathy, or Parkinson's disease

主要類別

化工/材料

細分類別

化工/材料應用

申請號碼

8940918

其他

State Of Development

Proprietary methods were used to identify, synthesize, and characterize seven, novel compositions of matter. Development included in vitro evaluation for specifications relevant to use in clinical practice, including: solubility, fluorescence characteristics, ability to cross the blood-brain barrier, binding constants, and capability to detect amyloidosis in brain tissue.

Intellectual Property Info

US and numerous foreign rights available for licensure in some fields. US application at link, below.

Related Materials

• Kevin Cao, Kevin, et al., Aminonaphthlanene 2-Cyanoacrylate (ANCA) Probes Fluorescently Discriminate between Amyloid-β and Prion Plaques in Brain, J. Am. Chem. Soc., Article ASAP, DOI: 10.1021/ja3063698, Publication Date (Web): August 6, 2012
• Sutharsan, J. et. al., Rational Design of Amyloid Binding Agents Based on the Molecular Rotor Motif, ChemMedChem, 5:1, 56-60 (2009).
• Ran, C., et al., Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as Near-Infrared Probes for In Vivo Detection of Amyloid-Beta Deposits, J. Am. Chem. Soc. 2009, 131, 15257-15261.
• Chang, W.M. et al., ANCA: A Family of Fluorescent Probes that Bind and Stain Amyloid Plaques in Human Tissue, ACS Chemical Neuroscience, DOI: 10.1021/cn200018v, Publication Date (Web): March 21, 2011.
• Dutescu, R. M. et al., Amyloid Precursor Protein Processing and Retinal Pathology in Mouse Models of Alzheimer’s Disease, Graefes Arch Clin Exp Ophthalmol (2009) 247:1213–1221.
• Cao et al. (2012), Amino Naphthalenyl-2-Cyano-Acrylate (ANCA) Probes Fluorescently Discriminate between Amyloid-β and Prion Plaques in Brain, J. Am. Chem. Soc., Just Accepted Manuscript, DOI: 10.1021/ja3063698, Publication Date (Web): August 6, 2012 

Additional Technologies by these Inventors

• Ultrasensitive, Ion Channel-Based Sensors
• pH-"Tunable" Nano-Particle Drug Delivery System
• Lead Compounds for Diagnosis and Therapy of Alzheimer's Disease

Tech ID/UC Case

20849/2010-162-0

Related Cases

2010-162-0, 2006-105-1, 2006-105-2, 2006-105-4, 2006-105-3, 2007-018-1, 2007-018-2

國家/地區

美國