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SignalRx to Present on its First-In-Class Triple CDK4-6/PI3K/BRD4 Inhibitor SRX3177 for Treating Cancer at the 13th Annual Drug Discovery Chemistry 2018 Meeting
  • USA - English


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iReachCompany

Apr 05, 2018, 12:31 ET

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SAN DIEGO, April 5, 2018 /PRNewswire-iReach/ -- SignalRx Pharmaceuticals Inc., a clinical-stage company developing novel small-molecules therapeutics via in-silico design to simultaneously inhibit multiple key orthogonal and synergistic oncotargets for the treatment of cancer, today announced the presentation of its novel triple CDK4-6/PI3K/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177.  The presentation by Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, will be at 2:20 pm on Thursday April 5th, 2018, in the Small Molecules for Cancer Immunotherapy session at the Drug Discovery Chemistry 2018 meeting in San Diego, CA.  Data related to combinatorial small molecules which strike multiple immune-oncology cancer targets and activate the innate and adaptive anti-tumor immune response will be presented.  The Small Molecules for Cancer Immunotherapy session will also be chaired by Dr. Durden.

Using SignalRx's proprietary CRIMP technology platform, the company designed SRX3177 to inhibit three key cancer-driving oncotargets with one drug: CDK4/6, PI3K and BRD4.  SRX3177 results in synergistic synthetic lethality in cancer cells (e.g., breast cancer, mantle cell lymphoma) because this novel anticancer agent addresses the following critical cancer-driving facts:

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  •      PI3K inhibition abrogates resistance to CDK4/6 inhibition.
  •      BRD4 inhibition decreases transcription of cyclin D1 and MYC.
  •      MYC inhibition decreases levels of immuno-oncology targets CD47 and PD-L1.
  •      CDK4/6 inhibition activates the AKT pathway.

"SignalRx designs all its novel chemotypes and drugs in silico.  Because not a single chemotype comes from screening commercially available compounds, SignalRx has built and continues to build a strong and proprietary pipeline" said Dr. Donald L. Durden, founder and senior scientific advisor of SignalRx Pharmaceuticals and Professor and Associate Director of Pediatric Oncology at the Moores UCSD Cancer Center.

The profile of in silico designed small-molecule triple inhibitor SRX3177 includes:

  •      Picomolar CDK4 inhibition potency.
  •      Double-digit nM PI3K and BRD4 inhibitory potency.
  •      BRD4-BD1 selective (5 X) vs BRD4-BD2.
  •      5 Fold more potent than Palbociclib as CDK4 inhibitor.
  •      19-80 Fold more potent than Palbociclib in 3 in vitro cancer cell assays.
  •      40 Fold less toxic in normal epithelial cells vs corresponding combination of three separate inhibitors (Palbociclib + BKM120 + JQ1).
  •      Induction of cell cycle arrest and increased apoptosis.
  •      Lethal in 85% of the cancer cell lines tested in NCI 60 cancer-cell panel.

"All our chemotypes are small molecules (no linking moieties used).  Because we rationally design all our anticancer agents from the beginning, we know how to tune in and out target affinity in our compounds.  We are in an excellent position to also explore CDK4/6-BRD4 and CDK4/6-PI3K single small-molecule inhibitors for cancer and other applications" said Dr. Joseph Garlich, SignalRx's Chief Scientific Officer.

SignalRx is also seeking partnering opportunities to accelerate the development of its programs and advance novel anticancer therapeutics into first-in-man clinical trials based on the promising profile and mode of action of its inhibitors. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to streamline their development alone and in combination therapies.

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, [email protected]

News distributed by PR Newswire iReach: https://ireach.prnewswire.com

 

SOURCE SignalRx Pharmaceuticals Inc.

iReach LastName, iReachCompany, 111-222-3333, [email protected]

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