EXTON, PA, United States
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Patent
Melior Discovery, Inc. | Date: 2016-08-08

The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising tenilsetam or pharmaceutically acceptable salts thereof that are useful in modulating inflammation. In particular, the compounds or pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder involving inflammation, including, but not limited to, delayed type hypersensitivity and contact hypersensitivity.


Naydenov A.V.,University of Washington | Horne E.A.,University of Washington | Cheah C.S.,University of Washington | Swinney K.,University of Washington | And 14 more authors.
Neuron | Year: 2014

The serine hydrolase α/β-hydrolase domain 6 (ABHD6) hydrolyzes the most abundant endocannabinoid (eCB) in the brain, 2-arachidonoylglycerol (2-AG), and controls its availability at cannabinoid receptors. We show that ABHD6 inhibition decreases pentylenetetrazole (PTZ)-induced generalized tonic-clonic and myoclonic seizure incidence and severity. This effect is retained in Cnr1-/- or Cnr2-/- mice, but blocked by addition of a subconvulsive dose of picrotoxin, suggesting the involvement of GABAA receptors. ABHD6 inhibition also blocked spontaneous seizures in R6/2 mice, a genetic model of juvenile Huntington's disease known to exhibit dysregulated eCB signaling. ABHD6 blockade retained its antiepileptic activity over chronic dosing and was not associated with psychomotor or cognitive effects. While the etiology of seizures in R6/2 mice remains unsolved, involvement of the hippocampus is suggested by interictal epileptic discharges, increased expression of vGLUT1 but not vGAT, and reduced Neuropeptide Y (NPY) expression. We conclude that ABHD6 inhibition may represent a novel antiepileptic strategy. © 2014 Elsevier Inc.


Ciallella J.R.,Melior Discovery, Inc. | Reaume A.G.,Melior Discovery, Inc.
Drug Discovery Today: Technologies | Year: 2017

In vivo phenotypic screening and drug repositioning are strategies developed as alternatives to underperforming hypothesis-driven molecular target based drug discovery efforts. This article reviews examples of drugs identified by phenotypic observations and describes the use of the theraTRACE® in vivo screening platform for finding and developing new indications for discontinued clinical compounds. Clinical proof-of-concept for the platform is exemplified by MLR-1023, a repositioned compound that has recently shown significant clinical efficacy in Type 2 diabetes patients. These findings validate an in vivo screening approach for drug development and underscore the importance of alternatives to target and mechanism based strategies that have failed to produce adequate numbers of new medicines. © 2017 Elsevier Ltd.


Reaume A.G.,Melior Discovery, Inc.
Drug Discovery Today: Therapeutic Strategies | Year: 2012

The tremendous biological complexity associated with living systems results in significant limitations on the reductionist or target-based drug discovery approach. Increasingly it is being recognized that allowing for more serendipity to enter drug discovery vis-a'-vis phenotypic screening provides for more cost-effective drug discovery with higher productivity. Several compelling studies and examples help establish this point of view. © 2011 Elsevier Ltd. All rights reserved.


Lipinski C.A.,Melior Discovery, Inc.
Topics in Medicinal Chemistry | Year: 2010

A medicinal chemist combines organic synthesis expertise and the ability to optimize chemistry structure-activity relationships (SAR) based on relevant biomedical information so as to achieve project goals. The ability to optimize chemistry SAR consists of both the easier to explain logical stepwise structural modification that is often described by quantitative structure-activity relationships (QSAR) and the more difficult to explain exercise of high-order pattern recognition. Optimizing SAR is full of traps for the unwary. What are the pros and cons of various types of screens? Should one believe the screening data? How does one optimize against multiple sometimes conflicting properties? What types of compounds are worth screening? How does one judge the quality of a screening hit? Very importantly, drug discovery is a team exercise in which the medicinal chemist plays a key facilitating role. Given good interpersonal skills, the medicinal chemist's training is broad enough to enable cooperative interactions across the whole discovery team. Chemistry pattern recognition is the unique skill that the medicinal chemist contributes to drug discovery. The ability to relate chemistry structure to biological activity and to change chemistry structure so as to change a variety of biomedical parameters in a desired direction leads to the successful "drug hunter." © 2009 Springer-Verlag London.


Patent
Melior Discovery, Inc. | Date: 2014-04-17

The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising tenilsetam or pharmaceutically acceptable salts thereof that are useful in modulating inflammation. In particular, the compounds or pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder involving inflammation, including, but not limited to, delayed type hypersensitivity and contact hypersensitivity.


Patent
Melior Discovery, Inc. | Date: 2014-08-29

The present disclosure describes compounds and pharmaceutically acceptable salts thereof and compositions and formulations comprising the same that are useful in methods of treating dyskinesia or related disorders, and methods for treating dyskinesia or related disorders.


Patent
Melior Discovery, Inc. | Date: 2015-05-01

The present disclosure describes compounds and pharmaceutically acceptable salts thereof and compositions and formulations comprising the same that are useful in methods of treating dyskinesia or related disorders, and methods for treating dyskinesia or related disorders.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 224.98K | Year: 2014

DESCRIPTION (provided by applicant): The goals of this project are to develop a biomarker for MLR-1023 in order to validate Lyn kinase as a molecular target for treatment of Type II diabetes (T2D) and use the biomarker to understand the pharmacokinetic/pharmacodynamic (PK/PD) disconnect in order to optimize a dosing regimen in clinical trials. These goals will be accomplished by showing MLR-1023 target engagement and kinetics of that engagement in cells and in a translatable rodent model of T2D. Results will be translated to human clinical studies. T2D is an epidemic in the U.S. that is worsening every year. The disease affects 8.3% of Americans, a rate that some expect to double by 2025. T2D was the seventh leading cause of death in 2007 and is a leading cause of a host of other disorders, including blindness and amputations. The disease takes a massive toll on the healthcare system, having caused about 174 billion in healthcare costs in 2007 alone. Although a host of therapies have been approved by FD


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