alexa Phenotypes Of A Novel Series Of 3-phosphoglycerate Dehydrogenase Inhibitors
ISSN: 2161-0444

Medicinal Chemistry
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

6th World Congress on Medicinal Chemistry and Drug Design
June 07-08, 2017 Milan, Italy

Nello Mainolfi
Raze Therapeutics, USA
Posters & Accepted Abstracts: Med Chem (Los Angeles)
DOI: 10.4172/2161-0444-C1-031
Abstract
PHGDH (3-phosphoglycerate dehydrogenase) is the first enzyme branching from glycolysis into the serine synthetic pathway and it oxidizes 3-phosphoglycerate into phospho-hydroxypyruvate using nicotinamide adenine dinucleotide (NAD) as cofactor. Increase in PHGDH expression at both mRNA and protein levels have been observed in nearly 70% of estrogen receptor-negative breast cancers; in addition a fraction of malignant breast and melanoma cells are dependent on elevated expression of 3-phosphoglycerate dehydrogenase (PHGDH). Furthermore, serine starvation has been shown to have a dramatic effect on tumor growth during in vivo mouse xenograft experiments. PHGDH has been a target of interest in the pharma/biotech industry for several years since the initial reports in early 2012 of its relevance in cancer where PHGDH amplified and overexpressing cancer cell lines have been shown to possess unique sensitivity to PHGDH knockdown that cannot be rescued by nutritional serine. The mechanisms underlying these studies have been subjected to intense investigation but remain unclear. We have been able to successfully identify first in class small molecule inhibitors of this target with nanomolar cellular potency, high degree of selectivity and oral bioavailability. In several cancer cell lines, these compounds inhibited glucose derived serine flux with nanomolar median inhibitory concentrations without significantly affecting glucose derived lactate. These compounds also inhibited glucose derived serine in animal studies and have the potential to be highly useful tools for understanding the role of PHGDH in tumor progression. The data presented here will provide unexpected insights on the role of PHGDH in serine biosynthesis and the dependency of cancer cells on PHGDH catalytic function.
Biography

Email: [email protected]

image PDF   |   image HTML
 
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords