Researchers from Zhejiang University and affiliated organizations have reported the discovery of novel orally bioavailable bromodomain-containing protein 9 (BRD9) proteolysis-targeting chimera (PROTAC) candidates for the treatment of acute myelocytic leukemia (AML). Synthesis and optimization led to the discovery of a novel series of BRD9 PROTACs, with compound [I] selected as the lead candidate with the best degradation and proliferation inhibition activities in vitro.
While early stage and involving a relatively small patient population, the interim phase Ib readout from the combination cohort testing estrogen receptor (ER)-targeting candidate vepdegestrant in combination with CDK4/6 inhibitor Ibrance (palbociclib) in heavily pretreated patients with ER-positive/HER2-negative breast cancer was impressive enough to prompt partners Arvinas Inc. and Pfizer Inc. to expand development work on the program. The results also struck a chord on the Street, with shares of Arvinas (NASDAQ:ARVN) gaining 31% on the day.
Work at Beijing Tide Pharmaceutical Co. Ltd. has led to the development of proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety coupled to an EGFR (HER1; erbB1)-targeting moiety through a linker.
A team at Berrybio (Shanghai) Ltd. has prepared proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety covalently linked to focal adhesion kinase (FAK)-targeting moiety through a linker.
Heat shock protein 90 (Hsp90) consists of four isoforms. Among them, the Hsp90α is overexpressed in advanced tumors and involved in tissue repair, tumor migration and metastasis as well. Researchers from Fujian Medical University (FJMU) reported on the discovery and preclinical characterization of [I], a selective proteolysis targeting chimera (PROTAC) acting as an Hsp90α protein degradation inducer for breast cancer treatment.
Bruton tyrosine kinase (BTK) inhibition is a provenly effective strategy for the treatment of B-cell malignancies with several compounds approved such as ibrutinib, acalabrutinib or zanubrutinib. BTK also plays a central role in immunity and has thus emerged as a potential therapeutic target in autoimmune and inflammatory disorders.
Tegid Therapeutics Inc. has identified proteolysis targeting chimera (PROTACs) compounds comprising cereblon (CRBN) ligands covalently bonded to a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)-targeting moiety.
Cancer Research Technology Ltd. has disclosed proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase binding moiety covalently bonded to a mitogen-activated protein kinase 7 (MAPK7; ERK5)-targeting moiety through a linker. They are reported to be useful for the treatment of cancer.
“I am not a fortune teller, nor am I a gambler. I will make no bets,” Lorraine Kalia told the audience at the 2023 International Congress of Parkinson’s Disease and Movement Disorders. “But I am optimistic.” At the meeting, which is being held in Copenhagen this week, Kalia, who is a scientist at Toronto Western Hospital’s Krembil Brain Institute and at the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases, was giving an overview of “Emerging targets in the clinic” in a plenary session on “Therapeutic strategies for the future.”
