Date: 2017-04-11
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: publication of results in Nucleic Acids Research
Company: 4SC (Germany)
Product: 4SC-202
Action
mechanism: histone deacetylase inhibitor (HDAC inhibitor)/lysine-specific demethylase inhibitor. 4SC-202 is an orally administered small molecule for the treatment of cancer. It affects gene expression via two well-known molecular cancer players. This epigenetic modulator inhibits both the lysine-specific demethylase (LSD1) and class I histone deacetylases (HDAC 1, 2 and 3), which play roles in the regulation of cancer signaling pathways. Through 4SC-202-mediated changes in the methylation or acetylation pattern of histone proteins (packaging proteins, around which the DNA is wrapped), expression of some genes is promoted, whereas expression of others is suppressed. These changes ultimately lead to more differentiation and less proliferation of cancer cells. The tumor ceases to grow and the immune system is then able to detect and destroy it.
Disease:
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On April 11, 2017, 4SC announced that 4SC's collaboration partner Prof. Steven A. Johnsen and his team at the Clinic for General, Visceral and Pediatric Surgery in Göttingen, Germany, published results from a preclinical study providing new insights into the epigenetic mode of action of 4SC's anti-cancer compound 4SC-202. (Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4- and MYC-dependent manner.
Nucleic Acids Research).
- Prof. Johnsen and his team conducted experiments in multiple pancreatic cancer cell lines. "Mechanistically we observed that the effects on the induction of gene expression mediated by 4SC-202 were elicited by the Bromodomain-containing Protein 4 (BRD4) and MYC, both of which are able to interact with the regulatory sequences located close to the target genes following the changes caused by treatment with 4SC-202," stated Prof. Johnsen.
- BRD4 is a well-characterized 'epigenetic reader' that recognizes and binds to acetylated lysine residues on both histone and non-histone proteins and plays an important role in maintaining cancer-induced transcriptional programs in the malignant cells. MYC on the other hand is one of the most studied human oncogenes and has been frequently associated with tumor growth and progression due to its involvement in a myriad of biological processes including cell growth, proliferation and cell death. 4SC plans to investigate this combination in cancer patients who are not responding to treatment with checkpoint inhibitors alone.
- • On March 21, 2017, 4SC announced that it will present two posters supporting the continued development of its product candidate 4SC-202, an epigenetic modulator that inhibits both the lysine-specific demethylase (LSD1) protein and class I histone deacetylase proteins (HDAC1, 2, 3), at the upcoming American Association for Cancer Research (AACR) Annual Meeting, being held on 1-5 April 2017 in Washington, D.C., USA. "In the first set of experiments, we investigated the anti-tumor activity and mode of action of 4SC-202, both as single agent and in combination with anti-PD1 and anti-PD-L1 antibodies, both checkpoint inhibitors, in immunocompetent and immunocompromised mice. 4SC-202 showed anti-tumor activity alone and synergized with checkpoint inhibition by stimulating the immune system and increasing the number of cancer-killing cytotoxic T cells in the tumor microenvironment. Most importantly, this was achieved without harming the viability of the anti-tumor T cells, which differentiates 4SC-202 from other HDAC inhibitors," summarized Frank Hermann, M.D., Chief Development Officer of 4SC."In the second set of experiments we investigated a different capability of 4SC-202: the ability to induce differentiation in acute myeloid leukemia (AML) cells, which is a therapeutic approach already in use to treat that disease. We evaluated the anti-tumor activity of 4SC-202 alone and in combination with various cytokines to identify a suitable combination," said Roland Baumgartner, Ph.D., Chief Scientific Officer of 4SC.
"Treatment with 4SC-202 alone induced differentiation in AML cells. In combination with the cytokine interferon-? (IFN-?), 4SC-202 induced an enhanced tumor-specific T-cell response that can act against residual malignant AML cells which additionally highlights the potential of 4SC-202 to boost anti-tumor immunity."
Is
general: Yes
