pipeline
An extensive pipeline of R&D programmes
Sentinel Oncology has developed a pipeline of small molecule drugs targeting cancer. We also have an interest in other rare brain disorders, with an advanced program to treat patients with fragile X syndrome.
Pipeline overview
Sentinel Oncology’s pipeline is built on our medicinal chemistry expertise focusing on small molecule inhibitors to treat a variety of cancers and other diseases.
SOL578 – Chk1
DNA damage occurs frequently in our day to day lives, introducing errors into the DNA of cells. Chk1 is part of the DNA damage response that has a crucial role in sensing and responding to that damage. Cancer cells are more reliant on Chk1 than normal cells and exploit this to avoid programmed cell death that would otherwise remove the cancerous cells. Inhibiting Chk1 is shown to force cancer cells towards death. Radiotherapy and chemotherapies such as gemcitabine work by causing DNA damage. Combining a Chk1 inhibitor with a DNA damaging therapy has the potential to enhance the effectiveness of chemotherapy and radiotherapy.
Sentinel Oncology’s candidate drug SOL578 has demonstrated preclinical activity both as a monotherapy treatment as well as in conjunction with chemotherapy agents, with activity across a broad range of cancer types, and it is being pursed in several indications including haematological and brain cancer. In 2022, Sentinel Oncology entered an exclusive worldwide licence agreement with PharmaEngine for the rights to develop and commercialise SOL578.
SOL784 – S6K1
S6K1 is a protein kinase involved in cell growth, survival and metabolism and contributes to several pathological conditions, such as cancer, Alzheimer’s disease, and tuberous sclerosis complex (TSC). S6K1 has also been implicated in fragile X syndrome (FXS), a genetic condition that causes intellectual disability, and behavioural and learning challenges. Inhibiting S6K1 in fragile X syndrome is proposed to correct pathophysiology’s associated with the disease and provide a therapeutic intervention to improve the lives of affected individuals and their families.
Our drug candidate SOL784 has demonstrated activity in FXS preclinical studies and is currently completing development work for this indication. Sentinel Oncology entered an alliance with the McQuade Center for Strategic Research and Development, LLC in 2021 to support the phase 1a and phase 1b clinical trials for SOL784 in FXS.
SOL686 – PLK1
PLK1 is an enzyme known to be involved in disease progression in many cancers. It plays a pivotal role in regulating mitosis, the process by which cells divide. In cancer, mitosis often goes wrong, and therefore targeting PLK1 in cancer cells can be used to treat this uncontrollable cell division. SOL686 acts by a novel mechanism, inhibiting PLK1 at an allosteric site - its polo-box domain. This is a unique site to PLK proteins, and makes SOL686 distinct from competitor PLK1 inhibitors as is predicted to offer several advantages in avoiding non-specific effects and drug resistance.
SOL686 has demonstrated activity in preventing tumor growth in preclinical systems, in particular for the brain cancer glioblastoma.
This program originated in the MRC labs in Cambridge, UK and was in-licenced from PhoreMost Ltd in 2017. We have now entered an exclusive option with an undisclosed partner to licence the wordwide rights.
Pre-candidate drug programmes
Sentinel Oncology has a number of programmes at earlier stages of preclinical activity. Our focus is on cancer targets that are well validated, where we can offer an advantage by developing drugs with superior chemical properties capable of crossing the blood brain barrier to treat brain cancers such as glioblastoma. Sentinel Oncology works with experts in specific brain cancer types at an early stage of each programme offering a preclinical platform that is highly disease relevant, leading to a higher chance of clinical success.
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