References
Nature Review Papers:
The glue degraders.
Garber, K.
Nat Biotechnol 42, 546–550 (2024).
Protein degraders push into novel target space.
Mullard, A.
Nature Reviews Drug Discovery 23, 799-802 (2024).
TPD Pioneering Discoveries from SEED Co-Founders:
Proposed role of ATP in protein breakdown: Conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis.
Hershko A. et al.
Proc. Natl. Acad. Sci. USA. 77(4): 1783-1786 (1980).
Role of the Ubiquitin-Proteasome Pathway in Regulating Abundance of the Cyclin-Dependent Kinase Inhibitor p27
Pagano M. et al.
Science 269(5224):682-5 (1995).
Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.
Huang L et al.
Science 286(5443):1321-6 (1999) – First E3 ligase structure solved.
Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex.
Zheng N et al.
Nature 416: 703–709 (2002). – First RING E3 ligase solved.
Mechanism of auxin perception by the TIR1 ubiquitin ligase.
Tan X. et al.
Nature 446(7136):640-5 (2007) – Coined “molecular glue”, from Prof. Zheng lab.
Defining molecular glues with a dual-nanobody cannabidiol sensor.
Cao S et al.
Nature Communication 13: 815 (2022) – Features of Nature’s “molecular glues” to increase binding between E3 and protein of interest, from Prof. Zheng lab.
Ewing Sarcoma is a severe unmet medical need with no new drugs for 30 years. This recent publication in 2023 showed 0% ORR:
Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.
Shulman DS et al.
Cancer Med. 12(14):15207-15216 (2023) – This combination showed objective response (ORR) at 0%, underscoring severe unmet medical needs in relapsed Ewing Sarcoma.
Targeting Ewing Sarcoma with A Novel RBM39 Degrader: DNA Damage Repair Pathway Effects (Abstract 1556)
Liu F. et al.
SEED AACR 2025 Presentation
RBM39 Biology:
Systematic pan-cancer analysis identifies RBM39 as an immunological and prognostic biomarker.
Zhang R, Wang W, Zhang N, Chen X, Liu W, Zhang L, Liu N.
J Cell Mol Med. 2022 Sep;26(18):4859-4871. doi: 10.1111/jcmm.17517. Epub 2022 Aug 21.
RBM39 Functions as a Potential Oncogene Through the NF-κB Signaling Pathway in Colorectal Cancer Cells.
Wang Y, Yang X, Yang Z, Chen Z, Jiang H, Wang Y, Shen D, Su G.
J Cancer 2025; 16(7):2233-2249.
