SAN DIEGO, CA, USA I April 19, 2016 I SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs through molecular design imparting multiple target-selected inhibition, today announced the presentation of scientific data on the company’s dual small-molecule PI3K/BRD4 inhibitor program in oncology. The presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, was made at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, LA.
The presentation highlighted advancements in the development of SF2523, SF2535 and SF2558HA, all single small molecules that inhibit both PI3 kinase (PI3K) and the new epigenetic cancer target BRD4. Key breakthroughs are:
- New crystal structures obtained for SF2523, SF2535 and SF2558HA with BRD4 protein providing insights on key dual inhibitor binding interactions.
- First-time proof of MYC inhibition by enhancing MYC degradation via PI3K inhibition AND blocking MYC production via MYC transcription inhibition (BRD4 inhibition).
- SF2523 exhibits desired in vivo anti-tumor effects with no toxicity in several mouse cancer models.
- Inhibition of PI3K-gamma and delta isoforms by SF2523 function as checkpoint inhibitors and enhance immune-therapeutics.
- BRD4 inhibition blocks tumor-specific super-enhancers activating the innate and adaptive immune response providing a novel strategy to treat cancer.
The company also demonstrated that SF2523 is safer to normal cells over the combination of single PI3K and BRD4 inhibitors making SF2523 an attractive anti-cancer candidate that can potentially overcome traditional toxicity issues associated with most combinations of oncology drugs.
SignalRx is also announcing that it is seeking a partner to accelerate the development of these novel small molecules into first-in-man clinical trials based on the promising profile of its PI3K/BRD4 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, e.g., kinome adaptation mediated by BRD4.
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).
SOURCE: SignalRx Pharmaceuticals
Post Views: 27
SAN DIEGO, CA, USA I April 19, 2016 I SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs through molecular design imparting multiple target-selected inhibition, today announced the presentation of scientific data on the company’s dual small-molecule PI3K/BRD4 inhibitor program in oncology. The presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, was made at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, LA.
The presentation highlighted advancements in the development of SF2523, SF2535 and SF2558HA, all single small molecules that inhibit both PI3 kinase (PI3K) and the new epigenetic cancer target BRD4. Key breakthroughs are:
- New crystal structures obtained for SF2523, SF2535 and SF2558HA with BRD4 protein providing insights on key dual inhibitor binding interactions.
- First-time proof of MYC inhibition by enhancing MYC degradation via PI3K inhibition AND blocking MYC production via MYC transcription inhibition (BRD4 inhibition).
- SF2523 exhibits desired in vivo anti-tumor effects with no toxicity in several mouse cancer models.
- Inhibition of PI3K-gamma and delta isoforms by SF2523 function as checkpoint inhibitors and enhance immune-therapeutics.
- BRD4 inhibition blocks tumor-specific super-enhancers activating the innate and adaptive immune response providing a novel strategy to treat cancer.
The company also demonstrated that SF2523 is safer to normal cells over the combination of single PI3K and BRD4 inhibitors making SF2523 an attractive anti-cancer candidate that can potentially overcome traditional toxicity issues associated with most combinations of oncology drugs.
SignalRx is also announcing that it is seeking a partner to accelerate the development of these novel small molecules into first-in-man clinical trials based on the promising profile of its PI3K/BRD4 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, e.g., kinome adaptation mediated by BRD4.
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).
SOURCE: SignalRx Pharmaceuticals
Post Views: 27
