Melior Discovery Publications

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

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

Phenotypic Screening
Macolino-Kane CM, Ciallellla, JR,Lipinski CA, Reaume AG
In: Drug Repositioning: Approaches And Applications For Neurotherapeutics.  CRC Press, June 2017.  Ed. Dudely J, Berliocchi L.

If you would like a pdf copy of this chapter please send a request to bizdev@meliordiscovery.com

A Mouse Model of Furosemide-Induced Overactive Bladder
Saporito MS, Zuvich E, DiCamillo A
Curr Protoc Pharmacol 2016 Sep; 74:5 68, 1-5

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

Rule of Five in 2015 and Beyond:  Target and Ligand Structural Limitations, Ligand Chemistry Structure and Drug Discovery Project Decisions
Christopher A. Lipinski
Science Direct, Elsevier, April 27, 2016

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

Parallel Worlds of Public and Commercial Bioactive Chemistry Data
Lipinski CA, Litterman NK, Southan C, Williams AJ, Clark AM and Ekins S.
J. Med. Chem. 2014 Nov; Article ASAP.

Computational Prediction and Validation of an Expert’s Evaluation of Chemical Probes
Litterman NK, Lipinski CA, Bunin BA, Ekins S.
J. Chem. Inf. Model., 2014 Sept; 54(10): 2996-3004.

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

The future of drug discovery: Two required supplements to current practices.
Reaume AG, Lipinski CA.
Pharma July 2013

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MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in-vivo.
Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG.
J Pharmacol Exp Ther. 2012 Jul;342(1):15-22.

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The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes.
Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS.
J Pharmacol Exp Ther. 2012 Jul;342(1):23-32.

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

Phenotypic in-vivo screening to identify new unpredicted indication for existing drugs and drug candidates.
Saporito MS, Lipinski CA, Reaume AG
in Drug Repositioning: Bringing New Life to Shelved Assets. (John Wiley & Sons, Hoboken, NJ, USA) 2012. Barratt MD and Frail D (Eds).

If you would like a pdf copy of this chapter please send a request to bizdev@meliordiscovery.com

Drug repurposing through nonhypothesis driven phenotypic screening.
Reaume AG.
Drug Disc. Today 2011 8(3-4):85-88.

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

theraTRACE^®: A mechanism unbiased in-vivo platform for phenotypic screening and drug repositioning.
Saporito MS, Reaume AG.
Drug Disc. Today 2011 8(3-4):89-95.

If you would like a pdf copy of this paper please send a request to bizdev@meliordiscovery.com

The anti-intellectual effects of intellectual property.
Lipinski CA.
Curr Opin Chem Biol. 2006 Aug;10(4):380-3.

If you are interested in learning more about Melior Publications, please contact bizdev@meliordiscovery.com to start the conversation.