Zeneth Brochure

™
Expert decision support software for predicting the
forced degradation pathways of organic compounds.
Introduction to Zeneth
Methodology
Degradant Identification
Zeneth is the expert knowledge-based software for
the prediction of forced degradation pathways.
The only actively maintained system for the
prediction of degradation, the software comprises of
a knowledge base of transformations implemented
by Lhasa’s scientific experts. Based on user
submitted query compound(s), these highly
transparent and scientifically robust predictions
provide the right level of information to support a
thorough review by experts.
Drawing on over 30 years of experience, Lhasa’s
expert scientists implement and regularly update
Zeneth transformations using public and proprietary
data, ensuring vast coverage of degradation
pathways. They use their expertise to analyse
complex, sometimes conflicting data and provide
expert reasoning rules to give you an indication of
how compounds are likely to be degraded.
Zeneth’s comprehensive knowledge of degradation
pathways ensure structure elucidation of experimentally
Degradation Assessment
Zeneth can swiftly provide
predictions for the likely degradation
seen degradants. Intuitive tools allow filtering of results
The following illustration provides an overview of how Zeneth
takes a query compound and provides a prediction:
based on chemical formula, mass and mass difference
allowing experimental data to guide predictions.
Structure of the starting material
Reaction conditions
products of query compounds whilst
taking into account the effect of
different excipients and impurities
Input
Maximum number of steps
Likelihood threshold
Expert ICH M7 Support
Perceive structural features
within the final formulated product.
Under ICH M7, potential degradation products likely to be
Structures of common excipients,
present in the final drug product should be evaluated for
with associated impurities are
mutagenic potential. Zeneth’s comprehensive transformation
provided for easy processing
library permits the identification of potential degradants.
alongside the query compound.
Analyse new degradants
and components for
possible further reaction
NO
YES
Meeting
Regulatory
Requirements
Numerous guidelines (ICH
Used by scientists across a range of industries,
Zeneth adds value in numerous stages of
compound and drug discovery.
Q1A/B, ICH Q3A/B, ICH
M7, RDC 58/2013 and
RDC 53/2015) stipulate
the need to understand
Has the
maximum
number of
steps been
reached?
NO
YES
Match transformations
present in the knowledge
base and generate degradants
Apply reasoning to
determine likelihood
Discard degradants whose
likelihood is below the threshold
Have all degradants
been processed?
Display Results
Structures of degradants displayed in a degradation tree
Structures of intermediates displayed in reaction path
Reaction name, comments, references and literature examples
Likelihood displayed (colour coded)
the consequences of
degradation, and focus
on impurities and stability
testing. The decision
support that Zeneth
Customisable Reports
offers can be invaluable
in meeting many of
Zeneth incorporates a reporting
these requirements.
framework that allows (.rtf .txt
WHY CHOOSE LHASA?
When asked why people choose to work with Lhasa Limited, the
common responses are:
.xlsx and .sdf) file export. Report
templates are fully customisable by
Early Screen for Toxic
Degradants
the end user.
Predicted degradants can be easily
Advanced Warning
System
Provides an instant
understanding of what
results might be expected
when running stress tests.
This additional information
can increase efficiency and
productivity by informing
decisions, aiding the design
of experiments and assisting
with excipient selection.
Software is easy to use and well supported.
exported, enabling analysis of
potential toxicity in Lhasa’s toxicity
Extensive Degradation
Knowledge
Transparency
Predictions are clearly
Sarah Nexus.
Drawing on over 30 years
detailed supporting
of experience, Lhasa expert
evidence associated with
scientists implement and
the degradation pathway.
regularly update Zeneth
Expert commentary,
transformations using
including a review of data,
public and proprietary data
mechanistic rationale and
ensuring vast coverage of
explanation of the structure
degradation pathways.
activity relationship are
predictions tools; Derek Nexus and
Transparency of Lhasa systems allows trust and
confidence in the science presented.
represented and contain
also included.
Meaningful Predictions
In addition to structural features, Zeneth
Over 30 years of experience in developing
state-of-the-art in silico prediction and
database systems.
accounts for a number of reaction conditions,
making its predictions consistent with the
conditions that have to be tested according
to the ICH guidelines: thermolytic, hydrolytic,
oxidative and photolytic.
All science is developed in-house, providing the
opportunity to discuss directly with Lhasa
expert scientists.
T: +44 (0)113 394 6020
To benefit from Lhasa’s
extensive degradation
knowledge, contact..
E: [email protected]
W: www.lhasalimited.org
Connect with us on LinkedIn
Who are we?
What makes us special?
Lhasa Limited is an active, scientific research organisation
working in chemistry and the life sciences. Our areas of
specialisation include the development of software for toxicology
and metabolism prediction and data management.
Lhasa Limited was founded on the basis of data and knowledge
sharing. Building on its reputation as the eponymous ‘honest
broker’, Lhasa Limited has continued to work on the basis of
‘shared knowledge, shared progress’ for more than 30 years.
Over this time, Lhasa has regularly been trusted with proprietary
data and this can be seen in the many successful consortia that
we continue to be involved in. The sustained success of such
consortia is demonstrative of how working with Lhasa has a
positive impact on the research and development process
of its members.
Working closely with Lhasa Limited members and the broader
scientific community, Lhasa continues to draw on over 30 years
of experience to create user-friendly, state-of-the-art in silico
prediction and database systems.
What do we offer?
Other Activities
Lhasa Limited has various collaborations including
elemental impurities, intermediates and Derek in
StarDropTM. Visit our website to find out more.
Derek Nexus TM
An expert rule-based system
for the prediction of toxicology.
Meteor Nexus TM
An expert rule-based system for
the prediction of metabolic fate.
Mirabilis TM
A tool for assessing the relative
purging of mutagenic impurities.
References
• Kleinman et al. (2014) In silico Prediction of Pharmaceutical Degradation Pathways: A
Benchmarking Study, Molecular Pharmaceutics. http://pubs.acs.org/doi/abs/10.1021/
mp5003976 • Parenty et al. (2013) An Expert System To Predict the Forced Degradation of
Organic Molecules, Molecular Pharmaceutics, 10 (8), pp. 2962-2974. http://pubs.acs.org/doi/
abs/10.1021/mp400083h
Sarah Nexus TM
A statistical-based system for
the prediction of mutagenicity.
Vitic Nexus TM
A chemical database and
information management system.
Reference 09/16
shared knowledge shared progress
Lhasa Limited Registered Office
Granary Wharf House, 2 Canal Wharf, Leeds LS11 5PS
Registered Charity (290866)
+44 (0)113 394 6020
[email protected]
www.lhasalimited.org
Company Registration Number 01765239. Registered in England and Wales. VAT Registration Number GB 396 8737 77.
ISO 9001: CERTIFIED