SignalRX Pharmaceuticals To Present At The AACR Annual Meeting On Its First-In-Class Triple PI3K/CDK4-6/BRD4 Inhibitor SRX3177 For Treating Cancer
Published: Apr 04, 2017
SAN DIEGO, April 3, 2017 /PRNewswire-iReach/ -- SignalRx Pharmaceuticals Inc., focused on developing novel small-molecule cancer therapeutics targeting key orthogonal and synergistic oncotargets, today announced the upcoming presentation of scientific data on the company's triple PI3K/CDK4-6/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177. The poster presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, will be poster #LB-298 at the April 5th late breaking poster session at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.
SRX3177 is developed on the rationale that concurrent PI3K inhibition can prevent resistance to CDK4/6 inhibition, and combined CDK4/6 and PI3K inhibition leads to synthetic lethality reported in a number of cancer types, including breast cancer and mantle cell lymphoma, and blocking the chromatin reader protein BRD4 downregulates MYC and cyclin D1 transcription, further promoting cell cycle arrest in G1.
The presentation will describe the discovery and early development of the molecularly designed small-molecule triple inhibitor SRX3177. Key highlights to be presented include:
- SRX3177's potent in vitro enzymatic inhibition profile (IC50: CDK4 = 2.54 nM, CDK6 = 3.26 nM; PI3Ka = 79.3 nM, PI3Kd = 83.4 nM; BRD4-BD1 = 32.9 nM, BRD4-BD2 = 88.8 nM).
- SRX3177 rational design based on thieno-pyranone scaffold and target modeling.
- Up to 82-fold more potent than palbociclib in a panel of mantle cell lymphoma, neuroblastoma, and hepatocellular carcinoma cell lines.
- 5-Fold more potent in cancer cells than combination of BKM120 (PI3K inhibitor) + palbociclib (CDK4/6 inhibitor) + JQ1 (BRD4 inhibitor).
- 40-Fold less toxic to normal epithelial cells than combination of BKM120 + palbociclib + JQ1.
- Cell cycle arrest and apoptosis induction with proven mode of action (p-AKT, p-Rb, chromatin release).
SignalRx is also announcing that it is seeking partnering opportunities to accelerate the development of this program and its PI3K-BRD4 program to advance novel small molecules into first-in-man clinical trials based on the promising profile of its inhibitors shown so far. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to develop them as single therapeutics and streamline their development in combination therapies focused on companion diagnostics built around synthetic lethality discoveries in human cancers.
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).
Media Contact: Guillermo Morales, SignalRx Pharmaceuticals Inc., 520-777-9609, firstname.lastname@example.org
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SOURCE SignalRx Pharmaceuticals Inc.