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Meeting Announcement
Date: Wednesday, September 28th, 2016
Topic: "Discovery of a Late Sodium Current Inhibitor, a Phase II Agent with Pre-clinical Anti-Ischemic and Anti-Arrhythmic Properties"
Speaker: Jeff Zablocki, Ph.D.
Senior Director
Gilead Sciences

The Holiday Inn
275 S Airport Blvd
South San Francisco, CA 94080
650-873-3550 | Map
Next door to the SSF Conference Center
Directions at


$50 before 9PM, Monday, September 26nd
$60 on-site
$40 full-time students pre-registration
$50 full-time students on-site
$3 service fee will be added to the pre-registration price

6:00 PM - networking
7:00 PM - dinner
8:00 PM - presentation

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Fisher Clinical
ReImagine Science
RHS Financial

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Late sodium current (Late INa) plays an important role in the pathophysiology of ischemia. It is increased during ischemia by reactive oxygen species that modify the Nav 1.5 channel C-terminus, resulting in an incomplete inactivation affording a persistent, or "late" current. GS-6615 (eleclazine), a novel, potent and selective inhibitor of Late INa is currently in clinical development for treatment of hypertrophic cardiomyopathy, Long QT-3 syndrome, and ventricular tachycardia – ventricular fibrillation (VT-VF). The first generation Late INa inhibitor ranolazine not only selectively inhibits Late INa compared to peak INa, but also inhibits IKr and beta-receptors. We will describe the structure activity relationship leading to the discovery of a potent Late INa blocker GS-6615 with a 10-fold selectivity over hERG. GS-6615 was 22 times more potent than ranolazine in reducing ATX-II induced prolongation of monophasic action potential duration with IC50 values of 0.72 and 16 µM, respectively. GS-6615 was 42 times more potent than ranolazine in reducing ischemic burden in vivo. In an ischemia induced model of VT-VF, GS-6615 inhibited the incidence of ventricular arrhythmias (VT and VF) from 65% and 75% respectively in control animals to 0%. GS-6615 represents a new class of potent Late INa inhibitors that will be useful in further delineating the role of inhibitors of this current in the treatment of patients with ischemic heart disease.


Jeff Zablocki is a Senior Director at Gilead Sciences Inc. where he leads a team of scientists working on targets in multiple therapeutic areas (cardiovascular, oncology, inflammation, and antiviral). Jeff and his teams over the years have produced 11 compounds that have entered clinical trials including a number of adenosine compounds: Regadenoson (A2A agonist, pharmacological stress agent, approved 2008), GS-6615 (Late INa inhibitor, LQT-3 arrhythmia, Phase III), GS-6201 (A2B antagonist, asthma, Phase II), and GS-9667 (Partial A1 Agonist, Type II diabetes, Phase I). Jeff has a strong commitment for drug discovery as exemplified by his being an inventor/author on 200 patents, publications, and presentations.

Jeff has served as the ACS MEDI Division Chair and is an ACS Fellow. Jeff has taught short courses on medicinal chemistry at: University of Illinois and York University (Toronto). Jeff received his PhD from the University of Illinois with Professor John Katzenellenbogen followed by a NIH post-doctoral study with Larry Overman at University of California, Irvine.

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