Epi-Drugs to Fight Cancer

Epi-Drugs

Lysine methylation has emerged in the last decade as a protein modification with expanding implications in a number of cellular processes, and the dysfunction of enzymes that regulate methylation are known drivers of cancer (i.e., lysine methyltransferases (KMT) and demethylases (KDM)). Given the involvement of methylation in a growing number of different biological processes, perhaps it is not surprising that the study of methylation events has been increasingly important in understanding basic cellular biology. As a result, there is a great interest to understand the biology of these methyl-regulatory enzymes, however, only a handful of KMT and KDM inhibitors (termed ‘Epi-drugs’)have been discovered or developed.

NuvoBio is currently investing significant effort toward expanding the commercial market of KMT and KDM inhibitors.

 

Epi-Drug Research Program

KDM5C – patented
Pre-clinical development

KDM5C was initially found to be important for brain development and function. We now know KDM5C abnormality is correlated with various cancers and is a key therapeutic target.

NuvoBio has completed initial toxicology and in vivo testing of a high affinity peptide inhibitor that maintains specificity.

SMYD3
Internal development

SMYD3 is critical for the activation of MAP3K2, a key kinase in the Ras-activated MAP signaling pathway, in both lung and pancreatic cancers.

NuvoBio is currently testing the cellular delivery and activity of several in vitro peptide inhibitors of SMYD3 in collaboration with key research partners.

NSD1
Internal development

Nuclear receptor binding SET domain protein 1 (NSD1) is frequently mutated in head and neck squamous cell carcinoma (HNSC), the sixth most common cancer by incidence, and a leading cause of cancer-related death.

NuvoBio has created an internal program for the development of NSD1 peptide inhibitors.

SETDB1
Internal development

Recent studies have implicated aberrant SETDB1 activity in the development of various types of cancers, including brain, head and neck, lung, breast, gastrointestinal, ovarian, endometrial and prostate cancer, mesothelioma, melanoma, leukemias, and osteosarcoma.

NuvoBio is collaborating to develop active inhibitors of SETDB1.

METTL13
Internal development

METTL13 is upregulated in cancer and negatively correlates with pancreatic and lung cancer patient survival. Loss of METTL13 markedly sensitizes cancer cells and xenograft tumors to drugs that target growth-signaling pathways.

NuvoBio has created an internal program for the testing and development of METTL13 peptide inhibitors.

KDM3A
Internal development

Lysine demethylase 3A (KDM3A) has been increasingly recognized as an important epigenetic regulator involved in multiple cancers. Elevated KDM3A is frequently associated with worse cancer prognosis

NuvoBio has created an internal program for the testing and development of KDM3A peptide inhibitors.