SignalRX Pharmaceuticals Presents In Silico Design Of Dual PI3K/BRD4 Inhibitors For Combinatorial Activation Of Anti-Tumor Immunity In Treating Cancer
Published: Sep 27, 2017
The presentation was entitled "A Novel Dual PI3K/BRD4 Inhibitor, SF2523 for Combinatorial Activation of Anti-Tumor Immunity in Cancer via the Orthogonal Inhibition of MYCN and MYC" and highlighted advancements in the development of single small-molecules that simultaneously inhibit both PI3 kinase (PI3K) and the new epigenetic cancer target BRD4 in vivo.
Key highlights presented are:
- Dual inhibitory chemotype disclosed which blocks MYC via two orthogonal independent pathways.
- Synergistic anticancer effects of dual inhibition: PI3K inhibition induces MYCN degradation and BRD4 inhibition blocks MYCN transcription.
- Dual PI3K/BRD4 inhibitor SF2523 blocks MYCN transcription and induces MYCN degradation
- SF2523 shown to block tumor growth, metastasis, and PI3K/BRD4 signaling in vivo.
- Demonstrated that SF2523 abrogates the macrophage immunosuppressive effects on tumor immunity via the blockade of the M1- M2 transition in vivo, and activates the adaptive T cell immune response against the tumor.
- Data also was also presented related to the recent discovery of SRX3207, a novel dual inhibitor which inhibits PI3K and a recently discovered new immune checkpoint kinase. This inhibitor has potent immunostimulatory properties and blocks the immunosuppressive macrophage compartment.
SignalRx, focused on developing more effective oncology drugs through molecular design imparting multiple target-selected inhibition, is also announcing that it is seeking partnerships to accelerate the development of their novel small molecules into first-in-man clinical trials. These molecules include single-targeted novel BRD4 inhibitors and CDK inhibitors with picomolar potencies.
About SignalRx Pharmaceuticals Inc.
SignalRx is a privately held corporation based in San Diego, CA developing small molecule inhibitors of key signaling pathways in cancer and cancer stem cells. The company has developed its proprietary CRIMP technology platform to develop new small-molecule therapeutics against more than one target molecule selected from the discovery of synthetic lethalities in cancer cells, epigenetic regulatory processes, immune checkpoints and DNA repair actions. SignalRx's research programs have novel dual inhibitors targeting critical onco-targets such as PI3K, MEK, BRAF, IDO1, IDH1, CDK4/6, Wnt, HDAC, DNMT, PARP and BET bromodomains. SignalRx is leveraging its expertise in novel multi-action inhibitors to develop enhanced anticancer therapeutics with improved efficacy, novel mechanism of action in a single molecule, and the potential to streamline their development (single agent, combination therapies).
Acknowledgement of NIH Support.
The project described above is supported by award number 2R42CA192656-02A1 from the NCI division of the NIH. The above description is solely the responsibility of SignalRx and does not necessarily represent the official views of the NIH or NCI.
Media Contact: Guillermo Morales, SignalRx Pharmaceuticals Inc., 520-777-9609, email@example.com