Oncology Drug Discovery

Targeted cancer therapies are being discovered and developed to treat a wide range of cancer patients. Domainex has a proven track record of delivering new therapeutic candidates that have progressed into clinical trials.

Genetic characterisation of tumour biopsies is driving personalised medicines, and in 2019, the FDA approved the third new cancer therapy for targeted treatment based on a specific genetic signature of a tumour instead of its site of origin.¹ Immuno-oncology – harnessing the body’s immune system to fight cancer – is also being actively researched.

Oncology at Domainex

At Domainex, our mission is to work with clients in the field of oncology to invent new drugs that will improve patient outcomes. Domainex scientists have worked successfully on a range of cancer targets at all stages of preclinical research from protein expression, protein crystallography and hit identification through to candidate nomination. Domainex has assisted in the delivery of an oncology clinical candidate, a pre-clinical candidate and several late-stage projects. We have worked in novel areas such as epigenetics and protein-protein interactions (PPIs), in addition to well-established target classes such as kinases.

Tankyrase

One example of an integrated oncology project is our collaboration with the Institute of Cancer Research (ICR) to identify inhibitors of Tankyrase. Domainex initially used its virtual screening platform, LeadBuilder, to identify hits. These hit compounds were then optimised by our medicinal chemists, in this case working closely with ICR biologists, which ultimately resulted in the nomination of a candidate drug. Click here to view the full case study.

Ras

Another example of an oncology project is a collaboration with The University of Oxford to develop inhibitors of the protein-protein interaction between RAS and its effector proteins. Domainex utilised its extensive experience of fragment-based drug design and structure-based drug design to develop a lead molecule with efficient binding to RAS.² Click here to view the full case study.

Methyltransferase, G9a

Domainex also led a drug discovery project to identify inhibitors of the lysine methyltransferase, G9a. Starting from a LeadBuilder virtual screen we identified potent, novel inhibitors which have potential as treatments for solid tumours. The lead compound demonstrated single agent efficacy in a tumour xenograft mouse model and can resensitise tumour cells to tamoxifen. Click here to view the full case study.

Acute Myeloid Leukaemia

Domainex has identified a first-in-class drug candidate that inhibits an undisclosed target that it has out-licensed to Invivoscribe  Inc. (San Diego, California, USA). Invivoscribe is responsible for the development of the drug candidate into a new therapy to treat patients with acute myeloid leukaemia. In return, Domainex shall receive milestones and royalties as the drug candidate progresses through clinical development, into  regulatory approval and ultimately upon its marketing as a new medicine. Click here to view the press release.

If you would like to access the Domainex expertise in oncology to support your own drug research programme we would be delighted to hear from you.

References

1. Advancing Health through Innovation: New Drug Approvals 2019
2. Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment E. Quevedo, Abimael Cruz-Migoni, Nicolas Bery, Ami Miller, Tomoyuki Tanaka, Donna Petch, Carole J.R. Bataille, Lydia Y.W. Lee, Phillip S. Fallon, Hanna Tulmin, Matthias T. Ehebauer, Narcis Fernandez-Fuentes, Angela J. Russell, Stephen B. Carr, Simon E.V. Phillips and Terence H. Rabbitts., Nat Commun 9, 3169 (2018)

Domainex press releases in the oncology field:

Queen’s University Belfast enters collaboration and licensing agreement with Ipsen to progress FLIP inhibitor project which has been supported by Domainex
26th January 2022

Novel first-in-class FLIP inhibitors for the treatment of cancer
28th March 2019

A new class of RAS-effector protein-protein interaction inhibitors
20th December 2018

Queen’s University Belfast and Domainex Win Late-Stage Award to Progress Novel Lung Cancer Drug Candidate into the Clinic
26th April 2016

University of Leicester scientist wins Domainex’s STAR Award to support her search for a treatment for non-Hodgkin lymphomas
3rd February 2016

Queen’s University Belfast and Domainex in Cutting-Edge Collaboration to Advance Novel Lung Cancer Drug Research
17th April 2015

UCB and Domainex collaboration provides valuable information on cancer drug target
12th March 2012