© 2015 by Zenobia Therapeutics Inc

October 5, 2018

The Fragment Based Lead Discovery Conference is right around the corner! This is the 10th anniversary of the meeting founded by Vicki Nienaber of Zenobia Therapeutics. This year, the meeting will be held on the beautiful island of Coronado CA at the Marriot Resort and Spa Coronado which is situated across the bay from the historic Gaslamp District.

I’m Erika Zehm, Director of Sales and Marketing for Zenobia Fragments but also a San Diego native. In honor of the 10th anniversary of the meeting and its return to San Diego, Zenobia Fragments, a San Diego based fragment library company, has put together the following tips and tricks to make the most out of your visit.

Getting to the Meeting:

The Marriot Resort and Spa Coronado is located at 2000 Second St, Coronado, CA 92118  about 11 miles from the San Diego International Airport. You have several transportation options.

San Diego is a Uber and Lyft friendly city. If you Fly into terminal two exit the baggage claim area, use the main crosswa...

September 20, 2018

So, you are contemplating your newest great idea for a product and are seeking investment ideally through the SBIR program.  To write a strong proposal, there are several key questions to consider beyond technical feasibility.

How have you validated your market? If you plan to partner with pharma, do you know that they will

buy it? Will Angels or Venture Capitalists invest in it? Do you know your Value Proposition?  What is your Product-Market fit?

These questions may seem abstract at this point but think about it, do you really want to build something that no one will buy?  Even if your goal is to cure a devastating disease, the reality is, unless you are independently wealthy, you will need cash and partners to progress through the clinic and to market. Once on the market, you will need doctors to prescribe your medicine and insurance companies to cover it.

Fortunately, NIH and NSF offer a program, I-Corps, to help you answer these questions! If you have been awarded a Phase I SBIR gran...

August 17, 2018

It’s that time of year again, we are back from summer vacation and thinking about submissions for the next NIH grant cycle.  First up is the SBIR deadline on September 5th. Here at Zenobia, since we are getting ready to submit our own SBIR grant and have products and services to generate preliminary data, we want to share our experience and learnings with the NIH SBIR system. Our last grant was accepted on the first try which is very uncommon for NIH.  We attribute that, in part, to learning from past mistakes and developing a grant submission process.

Over the years we have submitted several SBIR's and had very high success-rates with three NIH institutes and no success with a forth.  This very different success-rate gives rise to our first suggestion.  If you are having difficulties with one institute, you might consider repackaging your project and submitting to a different one!  As we discuss below, learn about the institute, talk to program managers, understand your review pan...

July 27, 2017

Why Screen as Mixtures?

In many cases, it is much more efficient to screen as mixtures because it pares down the dataset to a manageable range. One uses screening mixtures by soaking the crystal in a cocktail with multiple ligands. The secret to designing the proper mixture is to ensure that each ligand in the cocktail is differentiable from the other ligands, even at low resolutions. Express-Zen-Core288™ has a very high shape diversity, making it possible to group into shape diverse mixtures that can be distinguished at 2.7Å-3.0Å. 

How Does Zenobia Make it's Mixtures?

Zenobia's mixtures for crystallographic screening contain up to 6 compounds that are highly shape diverse permitting identification of the hit from the shape of the electron density map (Nienaber et al., 2000). For those that are not limited by crystals or beamtime, mixtures of 3 or single compound screening kits are also available for crystallography. Sample mixtures of 6 are depicted below.

...

July 20, 2017

What is Crystallographic Screening?

Crystallographic screening is a method used to detect ligands that bind to a target protein. What makes this metod special is that it also provides structural data about the binding location and interactions between the ligand and protein. The crystal itself has the protein molecules lined up in an ordered array with large solvent channels so that ligands can soak in and bind to sites on the crystallized protein. This method is exceptionally successful in detecting weakly binding ligands because the protein is highly concentrated in the crystal. Once the crystal has been soaked in the cocktail of ligands, diffraction data are collected and used to calculate an electron density map to determine if any of the ligands bound to the protein. If they do bind, one can tell by a visible positive electron density peak in a difference density map between the putative ligand protein complex and apoprotein. The ligand cocktails should be designed so that each lig...

April 6, 2017

PART 1: Fragments as a Pre-Screen to Assess Target Drugability

This is the first in a series of blogs discussing the concept of using fragment screening to assess target drugability (also termed ligandability in the literature). The idea of using a fragment pre-screen to assess the likelihood of identifying a compound for lead optimization is not a new one.  Because simple fragments have a higher probability of binding to targets than more complicated ligands (Hann et al., 2001), they are an ideal test-case for the drugability of a target.  Furthermore, because fragment-space (MW < 200) is estimated at 10 orders of magnitude less than drug-size space (MW < 450), a small fragment library will sample chemical space much more efficiently than a library of larger compounds (Edfeldt et al., 2011).  Applying this calculation to Zenobia’s Express-Zen-Core-288 compound fragment screen, for example, indicates using it as a drugability pre-screen would be like sampling ~2.88 trillion drug...

February 27, 2017

PART 3: How diverse are Zenobia's libraries?

This is the last in a three-part series discussing Chemical Diversity in fragment library design.  In