Histone lysine methyltransferases (HKMTs) are epigenetic targets implicated in tumorigenesis and cancer stem cell maintenance.
Imperial inventors have developed novel small molecule dual inhibitors of two key HKMTs: EHMT2(G9a) and EZH2, but not other HKMTs.
These are epigenetic targets implicated in tumorigenesis and cancer stem cell biology
Investigators have funding to progress preclinical development, lead optimisation, in vivo xenograft studies and biomarker validation
Seeking commercial parties interested in co-development and/or collaboration
The inhibitors reactivate epigenetically repressed genes in cancer cells, with activity in cells expressing wild-type EZH2
The dual G9A/EZH2 inhibitor HKMTI-1-005 induces chromatin changes that result in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family.
Treatment with HKMTI-1-005 improved the survival of mice bearing Trp53-/-null ID8 ovarian tumours and resulted in tumour burden reduction.
These small molecule inhibitors have potential for use in the treatment of neurodegenerative diseases such as Huntington's disease, viral conditions such as HIV, and cancers, including ovarian cancer, breast cancer, prostate cancer, liver cancer, skin cancer, bladder cancer, head and neck cancer, myelodysplastic syndrome, and solid and multiple haematological tumours (including glioblastoma, renal, esophageal, colon, non-small cell lung, small cell lung, multiple myeloma and chronic myeloid leukaemia tumours).
This technology is protected by patent PCT / GB2013 / 050689