Coinciding with the end of summer, we wrapped up the hit validation phase of our NPC lead discovery program. In 9 months, we whittled 50,o00 lead-like library compounds down to ~1,000 primary screening hits, which in turn we further winnowed down to ~100 fully validated hits, including several promising chemotypes with a completely novel and unexpected mechanism of action.
To kick off the month, Nina wrote a post on our blog that explains the unexpected connection between NPC and Ebola virus. You’ll be seeing more posts like this in future.
NPC1 is the gene responsible for Niemann-Pick C and the entry point of filoviruses like Ebola. How does that work? http://t.co/W5IxDRi3NO
— Perlara (@PerlaraPBC) July 31, 2015
We had a little fun on our IXM high content imager. Can you guess what you’re looking at? (Hint: it’s a tiny droplet)
— Nina DiPrimio (@NinaDiPrimio) August 7, 2015
Here’s the start of a tweetstorm where we extol the virtues of organism-based (versus cell-based) phenotypic screening.
5 reasons why model organisms (baker's yeast, nematodes, fruit flies, zebrafish) are better than cell-based approaches for drug discovery:
— Perlara (@PerlaraPBC) August 10, 2015
Maria, our summer intern, wrapped up her computational and experimental ALS yeast screen projects. The former will hopefully be submitted for publication later this year; the latter will hopefully be extended in followup work with grant support.
— Perlara (@PerlaraPBC) August 15, 2015
When not in lab, we’re out and about on the biotech networking circuit raising awareness about PLab and rare genetic diseases.
— Sangeetha Iyer (@IyerSangeetha) August 17, 2015
PLabbers in action at the bench!
— Perlara (@PerlaraPBC) August 19, 2015
With the help of our web dev Christy Collins, we relaunched our blog.
Our blog has a fresh, clean look: http://t.co/u2D27D0Vny
Tell us what you think! Thanks to @_chrisco for the redesign.
— Perlara (@PerlaraPBC) August 21, 2015
Sangeetha blogged about the different NPC mouse models that have been generated and studied over the years. We’ll be doing PK, GLP-tox and efficacy studies using the NIH NPC mouse model, which is a total loss of function. But we’re also interested in testing the I1061T knock-in NPC mouse created by Dan Ory’s lab.
I kept it short this time, by my standards anyway 🙂 https://t.co/ibEWDVIM6I
— Sangeetha Iyer (@IyerSangeetha) August 25, 2015
Our NPC screening funnel in 140 characters.
Our Niemann-Pick C drug screening funnel: 50,000 lead-like compounds ➞ 1,000 primary screening hits ➞ 100 validated hits ➞ 10 chemotypes.
— Perlara (@PerlaraPBC) August 27, 2015
September promises to be just as busy as August, with our first in vitro metabolic stability and in vivo PK assays on the docket. See you next month!