GNCK1a/CK1alpha degrading compounds (SJ-22-0028, SJ-21-0048)

St. Jude Reference #SJ-22-0028, #SJ-21-0048

Description

Researchers at St. Jude created small molecules that target protein degradation (PROTACs) of CK1alpha, IKZF1 and IKZF3 that can be used for the treatment of blood and solid tumor cancers. These compounds indicate greater potency over existing small molecules (lenalidomide). Additional compounds act through the modulation of cereblon, and all may be used for treating cancers, both hematological malignancies and solid tumors.

Keywords

small molecule, drug, PROTAC. targeted protein degradation, CK1alpha, IKZF1, IKZF3, hematological cancer, solid tumor, lenalidomide

Granted patents or published applications

Application filed, available under confidentiality

Related scientific references

Multidisciplinary research identifies novel targeted therapy for children with acute lymphoblastic leukemia

New chemical technology leads to better targeted therapeutics against high-risk leukemia in the lab

Gocho, Y., Liu, J., Hu, J. et al. Network-based systems pharmacology reveals heterogeneity in LCK and BCL2 signaling and therapeutic sensitivity of T-cell acute lymphoblastic leukemia. Nat Cancer 2, 284–299 (2021). https://doi.org/10.1038/s43018-020-00167-4

Lisa J. Alcock, Yunchao Chang, Jamie A. Jarusiewicz, Marisa Actis, Stanley Nithianantham, Anand Mayasundari, Jaeki Min, Dylan Maxwell, Jeremy Hunt, Brandon Smart, Jun J. Yang, Gisele Nishiguchi, Marcus Fischer, Charles G. Mullighan, and Zoran Rankovic, “Development of Potent and Selective Janus Kinase 2/3 Directing PG–PROTACs,” ACS Medicinal Chemistry Letters 2022 13 (3), 475-482, DOI: 10.1021/acsmedchemlett.1c00650 https://pubs.acs.org/doi/full/10.1021/acsmedchemlett.1c00650

Licensing opportunities

We are seeking partners to commercialize these small molecules.  Contact: chad.riggs@stjude.org

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.