St. Jude Reference #SJ-19-0047
Researchers at St. Jude have developed small molecule conjugates of JAK1/JAK2 inhibitor binders, which can be used for development of the treatment of CRLF2r and JAK-STAT driven ALL. CRLF2-rearranged ALL comprises up to 60% of Philadelphia-like (Ph-like, BCR ABL1-like) acute lymphoblastic leukemia (ALL), and up to 15% of B-ALL overall, and is associated with high risk features and poor outcome. Targeting of this pathway with type I JAK inhibitors such as ruxolitinib results in variable inhibition of signaling and proliferation in vivo, and emerging clinical data indicate suboptimal responses to ruxolitinib. Thus, new approaches to abrogate JAK-STAT signaling are urgently required to improve the dismal outcomes for CRLF2r ALL patients and may have broader therapeutic application in other JAK-STAT driven malignancies.
The researchers have advanced their studies to include several PROTACs based on multiple compounds and modified analogs (Ruxolitinib, Creblon, Baricitinib; and other conjugates), with 1,000x higher efficacy and improved results.
Small molecule, JAK1/JAK2 inhibitor binders, CRLF2r and JAK-STAT driven ALL, Ruxolitinib, Creblon, Baricitinib.
Granted Patents or Published Applications
A provisional patent application has been filed.
Related Scientific References
Published online, June 10, 2021: https://ashpublications.org/blood/article/doi/10.1182/blood.2020006846/476126/Degradation-of-Janus-kinases-in-CRLF2-rearranged
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