The recent approval of new tuberculosis (TB) drugs raises hope for new and more effective anti-tuberculosis treatment regimens. The Global Alliance for TB Drug Development (TB Alliance) is committed to ensuring that new anti-tuberculosis drugs fulfill the needs of patients, their families and the local health services that serve the communities. Here we present highlights of the TB Alliance's pipeline of regimen development, with novel regimens for patients with drug-susceptible, multidrug-resistant and extensively drug-resistant TB. The ongoing clinical trials (STAND, NC-005, Nix-TB and LIN-CL001) are outlined and their rationale and goals presented.

01 Dec 2010·Journal of Biological ChemistryQ2 · BIOLOGY

Nature of Pharmacophore Influences Active Site Specificity of Proteasome Inhibitors

Q2 · BIOLOGY

Article

Author: Matthew Britton ; Martijn Verdoes ; Paul P. Geurink ; Sondra L. Downey ; Alexandre A. Pletnev ; Annet E.M. Blom ; Wouter A. van der Linden ; Michael Screen ; Alexei F. Kisselev ; Martijn D.P. Risseeuw ; Herman S. Overkleeft ; Bogdan I. Florea ; Mathias J. Voges

Proteasomes degrade most proteins in mammalian cells and are established targets of anti-cancer drugs. The majority of proteasome inhibitors are composed of short peptides with an electrophilic functionality (pharmacophore) at the C terminus. All eukaryotic proteasomes have three types of active sites as follows: chymotrypsin-like, trypsin-like, and caspase-like. It is widely believed that active site specificity of inhibitors is determined primarily by the peptide sequence and not the pharmacophore. Here, we report that active site specificity of inhibitors can also be tuned by the chemical nature of the pharmacophore. Specifically, replacement of the epoxyketone by vinyl sulfone moieties further improves the selectivity of β5-specific inhibitors NC-005, YU-101, and PR-171 (carfilzomib). This increase in specificity is likely the basis of the decreased cytotoxicity of vinyl sulfone-based inhibitors to HeLa cells as compared with that of epoxyketone-based inhibitors.

01 Jul 1962·Annals of allergy

Clinical evaluation of compound NC-5 in various allergic conditions.

Article

Author: SWARTZ, H

100 Deals associated with NC-005(PanTherix Ltd.)

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Indication	Highest Phase	Country/Location	Organization	Date
Attention Deficit Disorder With Hyperactivity	Phase 2	-	PanTherix Ltd.	-

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