Powered by OpenAIRE graph
Found an issue? Give us feedback
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ IRIS - Università de...arrow_drop_down
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
versions View all 2 versions
addClaim

Rescuing Abandoned Molecules as Nav1.7 and PCSK9 Inhibitors

Authors: Amico G; Basile L; ROMEO, Giuseppe; SALERNO, Loredana; MODICA, Maria Nunziata; SIRACUSA, Maria Angela; MARRAZZO, Agostino; +2 Authors

Rescuing Abandoned Molecules as Nav1.7 and PCSK9 Inhibitors

Abstract

Academic institutions have plentiful of unexploited compounds. A cost-effective repositioning strategy from abandoned molecules coming from different research projects was applied. This strategy was based on the creation of a 2D-database then the biological assaying following adherence to the the Lilly OIDD (Open Innovation Drug Discovery) program by combining in silico methods and in vitro screening modules representing therapeutic areas of significant interest. The best results involve some molecules, that demonstrated to be active voltage-gated sodium ion channel Nav1.7 inhibitors. The inhibition of Nav1.7 is considered to be a potential mechanism for the treatment of chronic pain. Other findings refer to the inhibition of PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) synthesis, a convertase that plays a regulatory role in the metabolism of cholesterol. This work demonstrates that successful strategies can be established by mutual Academic-Industrial collaborations that can lead to the discovery and development of new drugs by a cost-effective approach by accessing complementary crucial skills and cutting-edge technologies, without costly investments to generate the highest quality data as efficiently as possible with small amounts of compound. Extracting latent value from abandoned molecules from various academic research projects, might be the starting point for innovative and cost-saving opportunities for both Academia and Industry to accelerate discovery of new drugs and disease treatments.

Academic institutions have plentiful of unexploited compounds. A cost-effective repositioning strategy from abandoned molecules coming from different research projects was applied. This strategy was based on the creation of a 2D-database then the biological assaying following adherence to the the Lilly OIDD (Open Innovation Drug Discovery) program by combining in silico methods and in vitro screening modules representing therapeutic areas of significant interest. The best results involve some molecules, that demonstrated to be active voltage-gated sodium ion channel Nav1.7 inhibitors. The inhibition of Nav1.7 is considered to be a potential mechanism for the treatment of chronic pain. Other findings refer to the inhibition of PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) synthesis, a convertase that plays a regulatory role in the metabolism of cholesterol. This work demonstrates that successful strategies can be established bymutual Academic-Industrial collaborations that can lead to the discovery and development of new drugs by a cost-effective approach by accessing complementary crucial skills and cutting-edge technologies, without costly investments to generate the highest quality data as efficiently as possible with small amounts of compound. Extracting latent value from abandoned molecules from various academic research projects, might be the starting point for innovative and cost-saving opportunities for both Academia and Industry to accelerate discovery of new drugs and disease treatments.

Country
Italy
Related Organizations
Keywords

Drug repositioning; database building; cheminformatics

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    2
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
Powered by OpenAIRE graph
Found an issue? Give us feedback
selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
Green
gold