adavosertib

Adavosertib (MK-1775) is a small molecule inhibitor of the checkpoint kinase WEE1 (IC50: 5.2 nM). It hinders the G2 DNA damage checkpoint.

ZNL 02-096 (Pomalidomide-C3-adavosertib) is a rapid and selective degrader of Wee1 (IC50=3.58 nM).ZNL 02-096 selectively degrades Wee1 at submolar concentrations without damaging PLK1, a secondary target of AZD 1775.ZNL 02-096 induces degradation of Wee1 and accumulation of DNA damage in MOLT-4 cells in vitro, In vitro in MOLT-4 cells, ZNL 02-096 induced Wee1 degradation, accumulation of DNA damage, cell cycle arrest in G2/M phase and apoptosis.ZNL 02-096 showed anti-proliferative effects in 300 cancer cell lines.

LEB-03-144 is a WEE1 DUBTAC (deubiquitinase-targeting chimera) linking AZD1775 (Adavosertib) to the OTUB1 recruiter EN523 through a C3 alkyl linker. LEB-03-144 shows significant WEE1 stabilization in HEP3B hepatoma cancer cells [1] .

LEB-03-146, a WEE1 DUBTAC (deubiquitinase-targeting chimera), effectively links AZD1775 (Adavosertib) with the OTUB1 recruiter EN523 via a PEG2 linker. This compound demonstrates considerable WEE1 stabilization in HEP3B hepatoma cancer cells [1].

LEB-03-145 is a WEE1 DUBTAC (deubiquitinase-targeting chimera) linking AZD1775 (Adavosertib) to the OTUB1 recruiter EN523 through a C5 alkyl linker [1] .

LEB-03-153 is a WEE1 DUBTAC (deubiquitinase-targeting chimera) linking AZD1775 (Adavosertib) to the OTUB1 recruiter EN523 through no linker [1] .