Treatment and inhibition of disease conditions using flexible heteroarotinoids
Patent Number: US7612107
Executive Summary:
General Description:
The majority of cancer-related deaths occur after primary therapy has been completed, mostly due to recurrence of the cancer or development of second cancers. Only agents that lack significant toxicity are acceptable in this setting. One of the most promising classes of cancer chemoprevention agents designated by the Chemoprevention Working Group to the American Association for Cancer Research (MCR) is retinoids. These compounds offer promise as cancer chemoprevention agents because of their abilities to regulate growth, differentiation, apoptosis, angiogenesis, metastasis and immune function. Despite limited success of various isomers of RA (All-trans-RA, 13-cis-RA and 9-cis-RA) and a synthetic retinoid in chemoprevention trials (Fenretinide, 4-HPR), structural alterations of the compounds are needed to improve the therapeutic ratio (efficacy/toxicity) before clinical application of a retinoid strategy for chemoprevention.
To reduce the toxicity of RA, researchers at the University of Oklahoma have come up with a new strategy to reduce the toxicity of arotinoids. Their strategy delays metabolic oxidation of the compounds by incorporation of oxygen or sulfur heteroatoms to replace one of the gem-dimethyl groups in the tetrahydronaphthalene ring of TTNPB. The resulting compounds, called Heteroarotinoids (Hets), exhibiting similar biological activities to RA, but significantly reduced toxicities. Additionally, inclusion of the heteroatom in the arotinoid structure has been shown to greatly improve the therapeutic ratio (efficacy/toxicity) in animal models. The clinical application of a Het called Tazarotene (produced by Allergan) for treatment of psoriasis, has confirmed the improved therapeutic ratio predicted for compounds with heteroatoms.
Strengths:
Weaknesses:
Patent Status:
Inventor Bio: Doris M. Benbrook
http://www.ouhsc.edu/benbrooklab/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Issued (Grant date: 2009-11-03)
- Patent Link: https://patents.google.com/patent/US7612107/
- Research Institute: University of Oklahoma
- Disease Focus: Among the diseases or conditions which can benefit from treatment with flexible heteroarotinoids as described herein are, (1) cancers and other diseases that involve abnormal differentiation, (2) diabetes, (3) hemophilia, (4) liver disease, (5) diseases involving human aldehyde dehydrogenase 2, (6) polycystic kidney disease, (7) lysosomal storage diseases, (8) high cholesterol, (9) obesity, (10) high triglycerides, (11) glycoprotein metabolism diseases, and (12) diseases involving abnormal angiogenesis
- Basis of Invention: Incorporation of oxygen or sulfur heteroatoms to replace one of the gem-dimethyl groups in the tetrahydronaphthalene ring of TTNPB, resulting in compounds called Heteroarotinoids (Hets)
- How it works: Heteroarotinoids exhibit similar biological activities to RA, but significantly reduced toxicities. Thus, inclusion of the heteroatom in the arotinoid structure was shown to greatly improve the therapeutic ratio (efficacy/toxicity) in animal models. The clinical application of a Het called Tazarotene (produced by Allergan) for treatment of psoriasis, has confirmed the improved therapeutic ratio predicted for compounds with heteroatoms
- Lead Challenge Inventor: Doris M. Benbrook
- Inventors: Benbrook; Doris M. (Oklahoma City, OK), Turman; Martin (Edmond, OK), Guruswamy; Suresh (Edmond, OK)
- Development Stage: Pre-clinical in vivo data
- Novelty: Reduced toxicity compared to similar classes of this compound (other RA compounds)
- Clinical Applications: A potential chemoprevention agent that is prescribed to cancer patients after primary therapy to prevent recurrence of the cancer or the development of new cancers
General Description:
The majority of cancer-related deaths occur after primary therapy has been completed, mostly due to recurrence of the cancer or development of second cancers. Only agents that lack significant toxicity are acceptable in this setting. One of the most promising classes of cancer chemoprevention agents designated by the Chemoprevention Working Group to the American Association for Cancer Research (MCR) is retinoids. These compounds offer promise as cancer chemoprevention agents because of their abilities to regulate growth, differentiation, apoptosis, angiogenesis, metastasis and immune function. Despite limited success of various isomers of RA (All-trans-RA, 13-cis-RA and 9-cis-RA) and a synthetic retinoid in chemoprevention trials (Fenretinide, 4-HPR), structural alterations of the compounds are needed to improve the therapeutic ratio (efficacy/toxicity) before clinical application of a retinoid strategy for chemoprevention.
To reduce the toxicity of RA, researchers at the University of Oklahoma have come up with a new strategy to reduce the toxicity of arotinoids. Their strategy delays metabolic oxidation of the compounds by incorporation of oxygen or sulfur heteroatoms to replace one of the gem-dimethyl groups in the tetrahydronaphthalene ring of TTNPB. The resulting compounds, called Heteroarotinoids (Hets), exhibiting similar biological activities to RA, but significantly reduced toxicities. Additionally, inclusion of the heteroatom in the arotinoid structure has been shown to greatly improve the therapeutic ratio (efficacy/toxicity) in animal models. The clinical application of a Het called Tazarotene (produced by Allergan) for treatment of psoriasis, has confirmed the improved therapeutic ratio predicted for compounds with heteroatoms.
Strengths:
- Reduced toxicity
Weaknesses:
- Has to be tested in larger clinical trials
Patent Status:
- Priority date: 2005-04-15
- Filing date: 2006-04-14
- Publication date: 2009-11-03
- Grant date: 2009-11-03
Inventor Bio: Doris M. Benbrook
http://www.ouhsc.edu/benbrooklab/
