WOBURN, MA, United States
WOBURN, MA, United States

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Patent
University of Oregon and Organix, Inc. | Date: 2015-07-31

Disclosed herein are compounds that bind to the vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions comprising those compounds, and methods of treatment using said compounds and pharmaceutical compositions.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 250.00K | Year: 2012

DESCRIPTION (provided by applicant): Abuse of methamphetamine (MA) is a major health problem. About 10 million Americans have used MA at least once. Chronic MA use has far reaching health consequences and has a tremendous societal impact. The National Institute on Drug Abuse has expressed considerable interest in the discovery of medications to address this problem. However, currently no medications are available for treatment of MA addiction. MA is a substrate for the Vesicular Monoamine Transporter-2 (VMAT2) located on intracellular storage vesicles in monoaminergic nerve terminals. The goal of this Phase 1 project is to design a potent and selective radioligand that reversibly labels the VMAT2 at a binding site that is coupled to functional activity of the VMAT2. A reversible [3H]ligand linked to functional activity f the VMAT2 will accelerate research toward discovery of medications for MA abuse. The unique ligands proposed here are designed to inhibit VMAT2 uptake by inhibition of the little explored [3H]reserpine binding site on VMAT2. A lead compound in the novel class of arylpiperidinylquinazolines (APQ) has already been demonstrated in our laboratories to bind reversibly at the [3H]reserpine binding site on the VMAT2. Optimization of this compound will now be achieved by sequential molecular modification with respect to binding potency at the VMAT2 and antagonist potency, as measured by inhibition of serotonin and dopamine uptake by the VMAT2. Further molecular modification will be conducted to optimize selectivity against competing binding sites. Topological changes will be introduced to explore the three-dimensional requirements of VMAT2 inhibition. Bioenantioselectivity of the VMAT2 binding site will be exploited by evaluation of enantiopure compounds. Compounds will be modified to optimize electronic, steric and lipophilic factors on functional and inhibitory potency at VMAT2. This project is expected to have a high impact on the search for MA pharmacotherapies as well as on the understanding of themolecular interaction of MA and potential medications that target the VMAT2. PUBLIC HEALTH RELEVANCE: Methamphetamine abuse, for which there are currently no medications available, has far reaching health consequences and a substantial societal impact. The goal of this project is to design radioligands as molecular tools to explore the interaction of methamphetamine with its biological target, the Vesicular Monoamine Transporter. These tools will accelerate the search for medications for methamphetamine addiction.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 178.15K | Year: 2016

Project Summary Abstract Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition The current drugs which are used to treat breast cancer focus on the reduction of the tumor size and have proven to be successful However currently there are no available treatment options which can effectively inhibit tumor invasion and metastasis Novel drug strategies therefore are needed to treat this chronic fatal and incurable condition Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id expression In the Phase segment of this Fast Track proposal our focus will be on developing lead compounds that display a favorable in vivo profile In Phase II segment of this proposal our lead compounds will be evaluated in multiple in vivo models We will also develop leads that display a favorable ADME Tox profile The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down regulation of Id Project Narrative Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition Currently there are no available treatment options which can effectively inhibit tumor invasion and metastasis The goal of this proposal is to develop a non toxic medication for the treatment and prevention of metastatic breast cancer


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 686.85K | Year: 2011

DESCRIPTION (provided by applicant): Catatonia is a widespread and serious syndrome characterized by mutism, stupor, refusal to eat or drink, posturing, and hypokinesis, and affects a broad range of psychiatric and other patients in the US and worldwide. Untreated or poorly managed catatonic patients suffer from a wide range of ailments including bed sores, deep venous thrombi, pulmonary emboli, urinary retention, infection, and aspiration pneumonia, which can lead to severe medical impairment and death. Existing treatments for catatonia including lorazepam (a benzodiazepine) often require high doses for an effective response, some patients are unresponsive, and chronic catatonia is poorly controlled. Discovery of a new treatment for catatonia would have a considerable commercial and scientific value. Our approach is to target an orphan drug receptor present in the cerebellum that is preferentially activated by lorazepam. We propose to carry out a Structure-Activity Relationship (SAR) program of synthesis andbiological evaluation of specifically designed lorazepam derivatives. From this project we specifically aim to discover one or more benzodiazepine analogs showing the desired in vitro orphan drug receptor potency and selectivity. In Phase Two compounds with a promising in vitro profile will be examined in vivo in knockout mice to confirm their mode of action. The best lead compounds will be further optimized and then evaluated in an animal model for catatonia. The long- term goal of this project is to discover a new, improved pharmaceutical agent for treatment of catatonia that can be licensed and developed for ultimate market approval. PUBLIC HEALTH RELEVANCE: Catatonia is a serious health problem in the Unites States, and the existing drug treatments are not always effective and have side effects. We are carrying out research to discover and develop a new drug to help these patients. If we are successful, doctors will have another option to help sufferers of catatonia.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 83.74K | Year: 2012

The project will develop a cost-effective strategy for disposing of manure produced on dairy farms by developing an affordable anaerobic digestion method that requires lower infrastructure investment and operating costs. This will lead to less reliance on traditional energy sources for dairies and reduced greenhouse gas emissions. It also will provide an additional revenue source for the farmer from the production of a high-value marketable soil amendment from the fiber resulting from this technology.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 82.00K | Year: 2010

This project addresses two issues important to agricultural producers. First, the high cost of implementing manure management strategies, such as installing and operating anaerobic digesters and therefore the need to optimize return on investment by developing value-added products from the residuals. Second is that biomass (particularly large quantities of agricultural residue like wheat straw, pea vines, and other residuals) has the potential to play a significant role in the future of combustion or co-combustion power plants. However, a drawback is that the overall energy yield of these materials is modest when compared to other potential sources. The project will develop a value-added industrial absorbent product from anaerobically-digested bovine manure fiber. In preliminary studies, fiber treated post-digestion to improve certain properties has shown significant promise as a superior absorbent for petroleum products. We will characterize and optimize these properties for several types of digesters. The optimized fiber absorbent will be delivered to test customers in order to evaluate its efficacy under industrial conditions and to survey customer satisfaction with the product. Following use, the fiber will be picked up from the customers and tested to determine its energy (BTU) content. This information will determine the potential of the product following use to absorb petroleum spills to augment the energy content of agricultural residues, thus making them a more efficient source of renewable energy.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 289.82K | Year: 2013

DESCRIPTION (provided by applicant): Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. The current first- line agents which are used to treat breast cancer metastasis primarily target tumor growth. These drugs produceonly modest increases in survival in patients with aggressive metastatic cancers and have significant side effects. Currently, there are no available treatment options that can specifically and effectively inhibit tumor invasion and metastasis. Therefore,novel drug strategies are needed to treat this chronic, fatal and incurable condition. Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id-1 expression. Id-1 is a key regulator of the invasive and metastatic potential of breast and additional cancers. In this Phase I proposal our focus will be on the optimization of our lead compound to discover one or more analogs that down-regulate Id-1 expression and consequently inhibit breast cancer cell invasion and metastasis. We will also optimize these compounds so that they display a favorable ADME-Tox profile. The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down-regulation of Id-1.PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. Currently there are no available treatment options which can effectively inhibit tumor invasion and metastasis. The goal of this proposal is to develop a non-toxic medication for the treatment and prevention of metastatic breast cancer.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 279.26K | Year: 2013

DESCRIPTION (provided by applicant): Chronic pain can result from various disease conditions and about 45% of the U. S. population seeks medical help for treatment of pain. Neuropathic pain is a type of chronic pain which is very difficult to treat, and most patients do not get adequate relief. A promising therapeutic drug target for the treatment of inflammation and pain is the cannabinoid CB2 receptor. In Phase I of this proposal our focus will be on the structural optimization of our lead template to develop a high efficacy CB2 selective agonist with pain suppression potential and with no CNS side effects. Established in vivo and in vitro pharmacological assays will be used to identify compounds that: 1) are highly selective for CB2 over CB1 receptors; 2)possess high efficacy and high potency in binding and activating the CB2 receptor; 3) possess high efficacy in reversing allodynia (i.e., nociceptive behavior in response to normally non-noxious stimuli); and 4) lack cannabimimetic side effects in whole animals that are typically indicative of CB1 receptor activation. The long-term objective of this proposal is to develop a novel drug for treatment of chronic pain which is both safe and effective. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE:8. Project Narrative Neuropathic pain is a type of chronic pain which is very difficult to treat since most patients do not get adequate relief with existing medications. The goal of this proposal is to develop CB2 receptor agonists with limited or no CNS side effects for the treatment of chronic pain.


Trademark
Organix, Inc. | Date: 2015-09-25

Horticultural soil amendments that are incorporated into or onto a turf, lawn or soil profile; Organic soil amendments; Soil amendments.


Trademark
Organix, Inc. | Date: 2015-04-29

Antibiotic ointments; Dietary supplements; Food supplements; Herbal supplements; Medicinal herbs; Medicinal oils; Nutritional supplements; Tincture of iodine.

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