Technologies

Challenge

The presence of cancer stem cells presents particular challenges to treatment in all cases. Certain cancerous stem cells are notoriously refractory to conventionaldrugs. Consequently, eradicating these cells is an important, unrealized therapeutic goal.

Solution

D ¹² -prostaglandin J _2/3 (D ¹² -PGJ ₃ ), a naturally formed metabolite of eicosapentaenoic acid (EPA), has been reported to selectively target and induce apoptosis of leukemia stem cells (LSC), but not normal hematopoietic stem cells in mouse spleen and bone marrow leukemic models. Treatment with D ¹² -PGJ ₃ induces unmitigated apoptosis of the LSCs in vivo—shown by the inability of donor cells from treated mice to cause leukemia in secondary transplants. Given the potent activities of D ¹² -PGJ ₃ , this invention describes procedures and new synthetic strategies for the synthesis of D ¹² -PGJ ₃ and D ¹² -PGJ ₃ analogs.

Technology Relevant Papers

K.C. Nicolaou et al, “Total Synthesis of D ¹² -Prostaglandin J ₃ , a Highly Potent and Selective Antileukemic Agent”, Angew. Chem. Int. ed. 2014, 53: 10443-10447.

K.C. Nicolaou et al, “Synthesis and Biological Investigation of D ¹² -Prostaglandin J ₃ Analogues and Related Compounds”, J. Am. Chem. Soc. 2016, 138: 6550-6560.

K.C. Nicolaou et al, “Total Synthesis of D ¹² -Prostaglandin J ₃ : Evolution of Synthetic Strategies to a Streamlined Process”, Chem. Eur. J. 2016, 22: 8559-8570.

Hegde et al, “D ¹² -prostaglandin J3, an omega-3 fatty acid–derived metabolite, selectively ablates leukemia stem cells in mice”, Blood J. 2013, 118: 6909-6919.

Kudva et al, “Evaluation of the stability, bioavailability, and hypersensitivity of the omega-3 derived anti-leukemic prostaglandin: D ¹² -PGJ ₃ ”, PLoS ONE 2013, 8(12): e80622.