Melior Discovery Publications

A Murine Model for Measuring Sebum Production That Can Be Used to Test Therapeutic Agents for the Management of Acne Vulgaris
Kathryn Boris, Muhammad Faizan, Robert J. Bendesky, Erin Davis, Andrew G. Reaume, and Wei-na Cong (2024)
Current Protocols, 4, e989. doi: 10.1002/cpz1.989

The paper details an innovative approach that we have developed as a model to evaluate acne therapeutic candidates

Preclinical. A Repurposed Novel Lyn Kinase Activator, MLR-1023, is a Model Example of Pharmacological Pleiotropy
Andrew G. Reaume and Christopher A. Lipinski (2022)
The Royal Society of Chemistry, 2022, ch. 10, pp. 196-220 https://doi.org/10.1039/9781839163401

This book chapter amongst a collection of works dedicated to drug repositioning presents the concept of “pharmacological pleiotropy”, that its existence is more common than most investigators appreciate, and that it is the “stuff” that provides drug repositioning opportunity.

Phenotypic screening of low molecular weight compounds is rich ground for repurposed, on-target drugs
Christopher A. Lipinski and Andrew G. Reaume (2022)
Front. Pharmacol. 13:917968. doi: 10.3389/fphar.2022.917968

This paper starts with a historical perspective of drug discovery dating back to the 19th century, and provides a rationale as to why phenotypic screening has historically been as productive as it has and why there likely remains untapped therapeutic potential among compounds less than 300 MWT that are generally overlooked as drug candidates because of their low MWT.

Drug Repositioning as a Pharmaceutical Strategy: The Obvious Benefits are Real but Beware of Pitfalls That May be Less Apparent
Andrew G. Reaume
Journal of Commercial Biotechnology (2021) 26(4), 104–5. doi: 10.5912/jcb1011

This paper chronicles the trials and tribulations, the successes and failures along the journey of developing a repurposed drug discovered through phenotypic screening. It a hopeful roadmap for others.

Why an In Vivo Screening Platform Covering Broad Therapeutic Spectrum is an Ideal Tool for Drug Repositioning: Illustrated by Discovery of a Novel Class of Insulin Sensitizers
Andrew G. Reaume and Christopher Lipinski
Phenotypic Drug Discovery: Chapter 12. (2021) Royal Society of Chemistry, https://doi.org/10.1039/9781839160721-00217

This book chapter lays out the rationale for why phenotypic screening is a cost-effective drug discovery tool and illustrates it with clinically validated examples.

MLR-1023 Treatment in Mice and Humans Induces a Thermogenic Program, and Menthol Potentiates the Effect
Rebello C, Coulter AA, Reaume AG, Cong W, Cusimano LA, Greenway FL
Pharmaceuticals 2021, 14: 1196. https://doi.org/10.1038/s41467-021-24784-4

This work represents a collaboration between the Greenway lab at the Pennington Biomedical Research Center and provides a mechanistic understanding of observations for weight loss first made by Melior in a phenotypic screen with MLR-1023 and subsequently in an MLR-1023 clinical study.

Cholride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis
Mayes-Hopfinger L, Enache A, Xie J, Huang C-L, Köchl R, Tybulewicz VLJ, Fernandes-Alnemri T, Alnemri ES
Nature Comm. 2021, https://doi.org/10.1038/s41467-021-24784-4

This paper, the PhD thesis work of Melior’s Lindsey Mayes-Hopfinger, uncovers new understanding in NLRP3 inflammasome activation.

High throughput in vivo phenotypic screening for drug repurposing: Discovery of MLR-1023 a novel insulin sensitizer and novel Lyn kinase activator with clinical proof of concept
Lipinski CA, Reaume, AG
Bioorganic Med. Chem, 2020, https://doi.org/10.1016/j.bmc.2020.115425

This paper is a narrative that describes the history of Melior’s candidate, MLR-1023, as well as the founding of Melior

In-Vivo Phenotypic Screening: Clinical Proof of Concept for a Drug Repositioning Approach
Ciallella JR, Reaume, AG
Science Direct, Elsevier, March 2017