|
| Status |
Public on Aug 11, 2017 |
| Title |
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs with in vivo activity in hematological malignancies [array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.
|
| |
|
| Overall design |
Transcriptome analysis of AML cell lines before and after treatment with a dual inhibitor against G9a and DNMTs.
|
| |
|
| Contributor(s) |
Agirre X, San José-Eneriz E, Segura V, Prósper F |
| Citation(s) |
28548080 |
| |
| Submission date |
Feb 25, 2016 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Xabier Agirre |
| E-mail(s) |
xaguirre@unav.es
|
| Phone |
+34 948194700
|
| Organization name |
CIMA
|
| Department |
Oncology
|
| Street address |
Pio XII, 55
|
| City |
Pamplona |
| State/province |
Navarra |
| ZIP/Postal code |
31008 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE78932 |
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs with in vivo activity in hematological malignancies |
|
| Relations |
| BioProject |
PRJNA313198 |
Less...
More...