Discovering and Developing SPEARs™ that Regulate Transcription of Oncogenic and Immune-modulatory Proteins

Transcription factors are proteins that have many roles in the human body. When dysregulated, transcription factors play a major role in oncogenesis and immune response by binding DNA at specific sequences to activate or inhibit gene expression. It is currently estimated that transcription factors represent approximately 20% of oncogenes .^1,2
Despite being considered “undruggable,” a better understanding of transcription factor regulation along with advances in therapeutic modalities have changed this hypothesis and opened new possibilities to utilize transcription factors as cancer drug targets.

Drugging Transcription Factors Requires a Tailored Approach to Disruption of Protein-Protein Interactions

Inhibition of specific transcriptional activity by disrupting transcription complexes represents a powerful approach to treating cancer. However, the nature of these complexes being protein-protein interactions (PPIs), along with their location inside of the cell or nucleus, create significant hurdles for conventional therapeutics and has been a long-standing industry challenge.

Traditional modalities – small molecules and antibodies – lack the properties required to effectively target transcription factors. We believe a tailored approach is required – we created SPEARs to address this problem.

1 Molecules 2018, 23, 1479; doi:10.3390/molecules23061479;
2 Cancers 2020, 12, 2296; doi:10.3390/cancers12082296