It has been previously demonstrated that while cancer cells with defects in ataxia telangiectasia mutated kinase (ATM) signaling are susceptible to ataxia telangiectasia and Rad3-related (ATR) inhibition following treatment with DNA-damaging drugs, normal cells can tolerate ATR inhibition by activating an ATM-mediated compensatory DNA damage response.
Auron Therapeutics Inc. has described proteolysis targeting chimeras (PROTACs) comprising a cereblon (CRBN) E3 ubiquitin ligase-binding moiety covalently linked to a histone acetyltransferase KAT2A and/or KAT2B (PCAF)-targeting moiety through a linker.
Haisco Pharmaceutical Group Co. Ltd. has prepared proteolysis targeting chimera (PROTAC) compounds comprising a cereblon ligase-binding moiety coupled to an EGFR (HER1; erbB1)-targeting moiety through a linker.
Astellas Pharma Inc. has patented new proteolysis targeting chimeras (PROTACs) comprising a cereblon E3 ubiquitin ligase-binding moiety coupled to GTPase KRAS (G12V mutant)-targeting agent through a linker.
Researchers from Zjengzhou University reported on the discovery and preclinical characterization of a novel PROTAC agent aimed at overcoming paclitaxel (Taxol) resistance in non-small-cell lung cancer treatment.
Chia Tai Tianqing Pharmaceutical Group Co. Ltd. has patented proteolysis targeting chimera (PROTAC) compounds comprising cereblon (CRBN) ligands covalently bonded to a Bcl-2-like protein 1 (Bcl-xl; Bcl-X; BCL2L1)-targeting moiety through a linker.
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.
