published preclinical data in Science Translational Medicine showing the beneficial effects of applying the Zalicus combination high-throughput screening (cHTS) technology for the potential treatment of ebolavirus (EBOV) infections. In the paper entitled “FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection,” the scientists, including drug developers from Zalicus and collaborators from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and investigators from the University of Virginia School of Medicine (UVA), describe screening a series of approved drugs and select molecular probes to identify drugs with antifilovirus activity.
“This whole approach is the reverse of how a molecular biologist might approach the problem,” White said. “If we’d gone with the molecular approach, we would never have looked at this class of drugs.”
Investigators discovered that a number of human-made drugs, including selective estrogen receptor modulators, or SERMS, blocked Ebola’s entry into cells in lab cultures and in mice.
But it wasn’t the estrogen drugs’ hormonal activity that thwarted the Ebola virus, preventing infection.
Rather, Johansen says it was the compound’s chemical structure, and the structure of a number of other drugs, that hindered the microorganism, something that surprised researchers.
“I think that’s one of the things that’s exciting…When we looked at our inhibitors, we found that a lot of them are entry inhibitors. And a lot of them have the structure even though the mechanism is for something completely unrelated,” Johansen said.
SERMS are so-called designer drugs designed to act like estrogen without negative side effects. For example, Tamoxifen is an older SERM used to treat breast cancer and the newer Reloxifen is approved for the prevention and treatment of the bone-weakening condition osteoporosis. But they have potentially serious side effects such as an increased risk of other types of cancer.
Johansen envisions using SERMS and other repurposed compounds in a number of situations to prevent infection and death.
“I think they could be used both by a civilian population where outbreaks are as well as potentially by the military if they were in an area where there was an outbreak and they went in to intercede, or if somebody used them for bio-warfare,” Johansen said.
I knew I should have paid attention in Chemistry class - I have no idea what what they're talking about. Did anyone know ZLCS was working on the ebolavirus? Do we even have that in this country? Didn't Dustin Hoffman and Rene Russo cure that thing back in 1999?
I thought they were all about going after the chronic pain market???
Slo: Do a bit of home work this. You'll find that its is one of the most deadly and horrifying of all viruses. One infected person getting into a non-effected area can create a pandemic in a very short period of time. Hence the Army's interest in a vaccine to protect troops from biological warfare, especially in the central African continent which is becoming more unstable daily. As well as the populations in general, home and abroad.
ZLCS signed a contract for services rendered, with the Army, for use of the cHTS program to look for solutions. If I remember correctly the contract was extended last year, I may be wrong on that but it would appear to be a lock to have it continued now due to the early success.
Chronic pain is still and I believe will remain the focus for a very long time.
Gazing into the crystal ball I see ZLCS spinning off the cHTS services for hire program in the next couple of years but retaining the use for in house discovery. Pure speculation.
Jim Long and calm
Sentiment: Strong Buy
Looks like they applied for the patent?
Publication number US20110028564 A1
Publication type Application
Application number 12/710,203
Publication date Feb 3, 2011
Filing date Feb 22, 2010
Quite alright...how about this news:
"Ibrutinib shows remarkable promise for treatment of mantle cell lymphoma"
"The ongoing trial of oral ibrutinib in patients with heavily treated relapsed or refractory MCL has maintained a response rate as high as 70 percent - better than any other single agent ever tested in the challenging disease - with milder side effects than other treatments."
More validation of the cHTS/Chalice program. Never was able to view the webcast for the presentation at the 2013 ARCC Annual meeting...so not really sure when Jensen/Pharmacyclics employed it's use, but I would imagine prior to the start of the Phase II study of Ibrutinib.
chevy: One key point is ZLCS got the patent, which would indicate that if it goes the distance its their puppy. I sort of assumed the Govt. would get that and farm it out. Looking good.
Jim Long and calm
Sentiment: Strong Buy
I was hoping to average down a little more. With the news we received today, where do you think the PPS will be tomorrow? Do you think we'll see .55 again or possibly .50 in the future?
“These data continue to confirm the potential of our combination high-throughput screening technology to identify drug combinations with activity in multiple disease states. The value of our cHTS technology, which has been previously validated in a number of cancer indications, continues to demonstrate promise in infectious disease applications as well,” commented Mark H.N. Corrigan, MD, President and CEO of Zalicus. “Our cHTS discovery collaborations with USAMRIID and UVA and pharmaceutical companies such as Novartis validate the value of the cHTS discovery technology to identify novel treatments for diseases.”
Key findings include:
Identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection.
Confirmed Anti-EBOV activity for both SERMs in an in vivo mouse infection model.
The SERM compounds inhibit viral entry and are not working through classical estrogen receptor-associated pathways.
These data support the screening of readily available approved drugs to identify therapeutics for the ebolaviruses and other biothreat infectious diseases.