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Small molecule therapeutics for hematologic malignancies

Small molecule inhibitors of a key cancer cell signaling pathway cause hematologic cancer cell death, but have low toxicity towards healthy cells. 

Technology Overview: 

Hematologic malignancies begin in blood-forming tissue, like the bone marrow or in the cells of the immune system. Non-Hodgkin lymphoma and leukemia were the 7th and 10th most diagnosed cancers in the US, respectively. New therapeutics for relapsed or refractory hematologic malignancies are needed as currently, there is no clinical standard of care for relapse of every type of hematologic malignancy. 

The Robertson group has developed a small molecule therapeutic for hematologic malignancies that inhibit a key cancer cell signaling pathway, causing cell death. This small molecule therapeutic has increased inhibitory action on cancer cells and decreased toxicity to healthy cells as compared to existing treatments. This results in a more specific mechanism of action that reduces the incidence of side effects such as nausea, fever, chills, and anorexia. The molecules are expected to be applicable to a broad range of hematologic malignancies.  

Advantages: 

  • Enhanced efficiency: 90% of cancer cells are inhibited post-treatment
  • Decreased toxicity to healthy cells
  • Decreased incidence of adverse events such as nausea, fever, chills, anorexia

Applications: 

  • Treatment of primary hematologic malignancies
  • Treatment of relapsed and refractory hematologic malignancies

 

The small molecule inhibitors are analogs of an existing hematologic malignancy therapeutic, with improved inhibitory effects on cancer cells and reduced toxicity to healthy cells. Multiple hematopoietic malignant cell lines were untreated or treated with #14, #15, #26, #31, or #1 compound (100nM) for 72 hours. Cell viability was determined by detecting luminescence. ALL, acute lymphoblastic leukemia; BL, Burkitt’s lymphoma; DLBCL, 817 diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; AML, acute myeloid 818 leukemia; MM, multiple myeloma; LCLs, lymphoblastoid cell lines. Tumor sizes were monitored in the mice after treatment of the indicated compounds. Tumor sizes at 12-day post-treatment with different analogs are highlighted. 

Stage of Development: 

Pre-clinical mouse models

Intellectual Property: 

U.S. Provisional Patent Application No. 62/890,207 filed August 22, 2019

Reference Media: 

Desired Partnerships: 

  1. License
  2. Co-development

Patent Information:

Inventors:

Erle Robertson
Wafik El-Deiry
Yonggang Pei
Yanming Du

Docket # 19-9029

For Information, Contact:

Neal Lemon
Associate Director, PSOM Licensing Group
University of Pennsylvania
nlemon@upenn.edu

Keywords:

Small Molecule