US 11,744,896 B2
Compositions, use, and method for CDK2-PROTACs for cancer therapy and hearing loss
Jian Zuo, Omaha, NE (US); Santanu Hati, Omaha, NE (US); Marisa Laura Zallocchi, Omaha, NE (US); Robert Hazlitt, Boulder, CO (US); and Jaeki Min, Memphis, TN (US)
Assigned to CREIGHTON UNIVERSITY, Omaha, NE (US); and ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC. (TENNESSEE NOT FOR PROFIT CORPORATION), Memphis, TN (US)
Filed by Creighton University, Omaha, NE (US); and ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC. (Tennessee not for profit corporation), Memphis, TN (US)
Filed on Sep. 28, 2021, as Appl. No. 17/488,080.
Claims priority of provisional application 63/084,090, filed on Sep. 28, 2020.
Prior Publication US 2022/0096642 A1, Mar. 31, 2022
Int. Cl. A61K 47/55 (2017.01); A61P 27/16 (2006.01); A61K 47/54 (2017.01)
CPC A61K 47/55 (2017.08) [A61K 47/545 (2017.08); A61P 27/16 (2018.01)] 7 Claims
 
1. A compound having the structure of Formula (1):
X-L-E  (1)
wherein X is a cyclin-dependent kinase 2 binding moiety;
L is a linking group selected from:
alkylene, (alkylene oxide)n-alkylene, —C(═O)-alkylene, —C(═O)-alkylene-(alkylene oxide)n-alkylene, —(C═O)-alkylene-O-alkylene, alkylene-(heteroaryl)-(alkylene oxide)m-alkylene-C(═O)—, and alkylene-(heteroaryl)-(alkylene oxide)m-alkylene;
wherein n and m are each independently an integer between 1 and 10; and
E is a ubiquitin ligase binding moiety, wherein X is selected from:

OG Complex Work Unit Chemistry
, wherein L is selected from:

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wherein n is an integer between 1 and 4, m is an integer between 2 and 4, and p is an integer between 0 and 4
and
, wherein E is selected from:

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wherein R8 is selected from:

OG Complex Work Unit Chemistry